Dosing of Medications for ADHD

We consider the approach described below to be fundamentally sound. However, these are merely considerations from a scientific perspective and cannot serve as therapeutic recommendations for individual cases.
In any case, a personalized treatment plan must be developed by a doctor or psychotherapist.
This information is not intended to encourage self-medication, but rather to help people with ADHD and their families better understand medical recommendations and to enable them to discuss the options described with their treating physician and therapist.
Each specific treatment must follow the instructions of the attending physician for that particular case.

Optimal medication for ADHD often requires a highly individualized and finely tuned dosage and adjustment. A purely formulaic approach to medication is not possible for ADHD.
Determining the optimal dosage of medication for ADHD depends on the type of medication.

The first clinical trials for dosing in ADHD are currently underway.¹

1. Medication selection¶

For more information, see Choosing a Medication for ADHD or ADHD with Comorbidities

2. Dosage of Stimulants¶

2.1. Basics of stimulant dosage¶

In general, up-dosing that starts with low doses and increases them flexibly and individually offers a clear advantage over administering fixed doses.² This has been known since the 1970s³ and is confirmed by a new, comprehensive meta-analysis⁴. Studies also use a slow up-dosing approach to avoid side effects.⁵
With both MPH and AMP, as the dose increases, both efficacy and the likelihood of discontinuation due to side effects rise. In fixed-dose studies, the additional efficacy benefit declined starting at 30 mg of MPH or 20 mg of AMP.

More is not necessarily better. For each person with ADHD, the appropriate dose—one that provides optimal symptom relief with minimal side effects—must be determined through trial and error.⁶

The fact that the fixed-dose approach—which is clearly less suitable in clinical practice—is still sometimes used appears to stem in part from the FDA’s requirement for fixed-dose studies as part of the drug approval process. However, these approval studies are not designed with clinical practice in mind.
To determine the lower limit of the therapeutic range, study designs in which different patient groups each receive doses that result in a previously defined blood concentration range of the drug are more appropriate.⁷ The clozapine study by VanderZwaag et al. was cited as a positive example.⁸ Due to the logistical challenges and resulting costs, fixed-dose studies are preferred for determining the lower limit of the therapeutic reference range.

The guidelines in Germany and the United States do not specify fixed doses but instead call for up-dosing.
In our experience, it is advisable to take a more gradual approach than the one outlined there.

2.1.1. Immediate release or sustained release stimulants¶

A single dose of MPH can be administered using either immediate release MPH or sustained release active ingredients.
A single dose of immediate release MPH is common. A single dose of sustained release MPH is also recommended.²³ The physician will have to weigh the disadvantage of more frequent dosing with immediate release MPH—since only regular dosing ensures a consistent effect without rebound—against the advantage of more precise dosing when administered by sufficiently responsible patients. This issue generally does not arise in school-age children.

Given the positive experiences of adults with ADHD, we expect that Vyvanse will likely become the standard treatment for adults in Europe in the future. So far, however, this is only possible off-label or with a private prescription.
In the United States, once-daily dosing with long-acting amphetamine salts is common (Adderall XR).

2.1.2. Initial dose¶

In general, the appropriate dose must be determined individually for each person with ADHD. Therefore, studies that statistically determine the “optimal” dose of stimulants are of limited use for individual treatment.
Stimulants have dose-dependent effects.²⁴

• Low doses selectively activate norepinephrine and dopamine neurotransmission in the PFC (working memory, executive functions, inhibition, emotion regulation)
• Higher doses increase the efflux of dopamine and norepinephrine throughout the brain, thereby also affecting the striatum (drive, motivation). Attention problems in ADHD arise primarily from a lack of self-motivation (which is why attention works for intrinsically interesting things but not for intrinsically uninteresting ones). Since stimulants at higher doses also increase dopamine and norepinephrine in the striatum, they consequently boost drive and attention. Atomoxetine, which increases dopamine only in the PFC, has barely any such effect.

In general, stimulants are administered at the lowest available doses. Currently, these are 2.5 mg of immediate release MPH by splitting higher-dose tablets, 5 mg for MPH half-day extended-release formulations, 18 mg for Concerta, 5 mg for Adderall XR capsules, etc. The dose is then increased in equal increments until the optimal benefit is achieved. At the dose that provides optimal symptom improvement, most adults with ADHD report only a few side effects other than a mild and temporary loss of appetite.⁶
In 2002, the American Academy of Child and Adolescent Psychiatry (AACAP) recommended a starting dose of 5 mg for MPH and 2.5 mg for dextroamphetamine or mixed amphetamine salts, all in immediate release form, taken in 2 to 3 daily doses.¹⁵
The EMA recommends starting treatment with MPH at the lowest possible dose.⁹

• low starting dose (2.5 mg of immediate release MPH / single dose or equivalent dose of other medications)²⁵²⁶ , or 5 mg of half-day immediate release MPH²⁷
• at least 5 days per dose level
• Dosage increments: max. 2.5 mg of unret. MPH per single dose
• The optimal dose varies greatly from person to person²⁵²⁶
• Effect of slow dosing:
  • reduces side effects
  • prevents patients from missing the correct dose due to the sometimes very narrow therapeutic range²⁵²⁶

In Germany, a single dose of 5 mg of immediate release MPH was recommended for school-age children in 2004. ²⁸ At that time, this was the lowest available dose of MPH. It was not until two years later that the first 5-mg half-day sustained-release formulation (Medikinet retard 5 mg) was approved.

The equivalent of 5 mg of immediate release MPH in Vyvanse is 10 mg. When titrating in 2.5 mg increments of immediate release MPH or 5 mg increments of sustained release MPH, the corresponding equivalent is 5 mg increments of Vyvanse.²⁹³⁰ Another conversion table, specifically for U.S. formulations, can be found in Stutzman et al.³¹
The manufacturer’s recommended starting dose of 30 mg for lisdexamfetamine was not determined in clinical trials. The manufacturer has not conducted any studies with starting doses lower than 30 mg. The setting of the starting dose at 30 mg is therefore based solely on regulatory considerations. It is not supported by any pharmacological studies.

A collection of single-dose standards for various American ADHD medications by Lurie A, Lurie RH, Children’s Hospital of Chicago (2024) can be found in Romba et al.³³

2.1.3. Dosing increments: Small increments are better than large ones¶

Treatment for ADHD in children begins with a low dose, which is then gradually increased

In our view, smaller increment up-dosing offers a clear advantage over the currently standard up-dosing in 10 mg/half-day sustained-release MPH dose increments, which is the basis for the following dosing recommendations. The typically recommended duration of each step—7 days—can thus be shortened to 4 to 5 days, so that the overall rate of up-dosing changes only slightly.

Mutschler also recommends starting with a low dose and increasing it gradually.³⁴
“Unwanted side effects are most likely to occur at the start of treatment, which is why the dosage should be increased gradually.”³⁵
Although about three-quarters of people with ADHD who were treated with MPH experienced no side effects whatsoever³⁶, this rate should nevertheless be reduced through slow titration.

Slow titration of ADHD medications in small dose increments serves several purposes:

• Low doses of stimulants have a different effect and target different regions of the brain than high doses
  • Low-dose MPH has a noradrenergic effect only; dopaminergic effects are attained only with higher-dose MPH. For more on this, see Mechanism of Action of Methylphenidate in the article MPH Part 1: Active Ingredients, Effects, Response.
  • Low doses of D-amphetamine (ranging from 0.5 to 1 mg/kg in rats, which corresponds to approximately 0.2 to 0.6 mg/kg in humans) reduce (hyper)activity, while higher doses increase drive³⁷
  • Norepinephrine and dopamine play very closely related roles in improving ADHD symptoms. What works best for a person with ADHD must be determined on an individual basis.
  • Even in cases of severe symptoms, a very low dose may be appropriate on an individual basis.³⁸ Huberman reports a single case in which an optimal daily dose of 2.5 mg of Adderall was effective (a woman weighing 150 kg).³⁹ A dose of 0.3 mg/kg showed greater improvement in learning tasks among children with ADHD than 1 mg/kg; 1 mg/kg resulted in better social ratings by teachers and less restlessness in hyperactive children, but poorer academic performance than placebo.⁴⁰ We know several people with ADHD for whom a single dose of 1.25 mg of immediate-release MPH is optimal.
• Gradually acclimating the body to the active ingredient to avoid side effects that could lead to an avoidable discontinuation of ADHD medication.⁴¹⁴²
• A dosage that is too high leads to a recurrence of the ADHD symptoms that are prevented at the appropriate dosage (inverted-U curve).⁴³
• Adverse side effects increase significantly when the dose exceeds the optimal level.⁴⁴

However, we have also received isolated reports from people with ADHD in whom low doses caused severe side effects that disappeared at higher doses. We do not know, however, whether the side effects resulted from the low dose or from the initial administration itself.

2.1.4. Duration of each dosing increment: 5 to 7 days per increment¶

From a purely pharmacological standpoint, the dose could be increased rapidly, since stimulants take effect immediately upon reaching the brain. From a clinical perspective, the dose could be increased daily, since all effects and side effects of an immediate release dose become apparent 1 hour after ingestion. Once the dose wears off, there is no further or cumulative benefit.⁶
In our view, however, there are several arguments that clearly speak against daily up-dosing:

• The effects of sustained-release medications must be monitored throughout the day
• It is not the doctor who assesses the effect, but the people with ADHD themselves
• People with ADHD have no experience and therefore don’t know what to look out for
• People with ADHD may experience placebo effects, which depend heavily on their subjective attitude toward the medication and can only be distinguished from the actual effect after several days
• Individual daily factors can skew the results
  • Rule of thumb: monitor daily, but evaluate only the 3-day average
• For women, the current stage of the menstrual cycle must be taken into account
• The longer a medication’s effects last (extended-release, prodrug), the longer the increments should be. With lisdexamfetamine, steady state is apparently reached on day 5.⁷⁶ In slow metabolizers, this period is significantly longer. The consequences are that, when initiating treatment with lisdexamfetamine (Vyvanse), dose titrations should not be performed more frequently than once a week.
• However, increasing the dose in increments of several weeks does not improve titration (especially not with methylphenidate) and merely prolongs the time it takes to reach the appropriate dose. More often than not, this simply places an unnecessary strain on the already limited persistence of people with ADHD.

Therefore, 1-day dose increments are not recommended for MPH either. This applies even with a single daily dose, although the duration of the increments can be reduced in that case.
For MPH, the duration should be at least 4 days, but should not be unnecessarily extended.

Due to its long-lasting effect, dextroamphetamine reaches a steady state. Steady state appears to be reached on day 5.⁷⁶ The consequences are that, as with dextroamphetamine, dose titrations for lisdexamfetamine should not be conducted at intervals shorter than one week.

We recommend that people with ADHD keep daily records of their medication intake, symptoms, and side effects (e.g., using the dosage guide from the ADHD forum on AdxS.org), but never to evaluate them on a daily basis; instead, always calculate a 3-day average. It follows that an increment of Level 3 to 4²⁸ (we mean: more like 5 to 7) days are needed to allow for an assessment.
We do not consider the 1-month duration of each dose adjustment phase, as practiced by some doctors, to be very sensible. It offers no advantages and may be necessary only to compensate for dosing increments that are too large.

A German dosing regimen for school-age children using immediate-release MPH was as follows:²⁸ However, this recommendation dates from 2004, when 5 mg of immediate-release MPH was the smallest available dose of MPH and the extended-release formulations now in use had not yet been developed. It was not until two years later that the first 5-mg half-day-release formulation was approved (Medikinet retard 5 mg, 2006).)

Duration	Morning	Noon
3 days	5 mg	-
4 days	10 mg	-
Medical Consultation for Assessment
5–8 days	10 mg	5 mg
Further individualized dose titration in 5- to 8-day increments

Most children need 10–20 mg in the morning and 5 to 10 mg in the early afternoon.
If necessary, take 3 doses: in the morning, late morning, and afternoon.

2.1.5. Target dose¶

The optimal dosage of an active ingredient and formulation that is suitable for a person with ADHD must be determined individually in two dimensions:⁷⁷

• Single-dose amount
• Number of daily doses

2.1.5.1. Target Factor 1: Single-Dose Amount¶

In our view, the “optimal dose” should be the lowest dose that produces an optimal therapeutic effect. Some guidelines, however, recommend the dose at which no further improvement is observed.⁴⁴ In our opinion, this approach overlooks the fact that two different doses can have equally good effects. Given that approximately 30% of people with ADHD discontinue their medication within 12 months and about 50% within 2 to 3 years⁷⁸ —and even more so among children and adolescents,⁷⁹⁸⁰ —priority should be given to minimizing side effects as much as possible.

Since there are marked individual differences in dose-response patterns, the optimal dose must be determined on an individual basis. In this regard, the art of treating patients with MPH (and stimulants in general) goes far beyond simply “fine-tuning the dosage.”⁴⁴

2.1.5.1.1. Dosage should not be determined on a blanket basis or based on body weight¶

The optimal target dose for ADHD varies greatly from person to person and cannot be determined on a one-size-fits-all basis.

Fortunately, the misconception that stimulants should be dosed in relation to body weight is now less common.
Since the percentage of methylphenidate that reaches the bloodstream varies from person to person between 11% and 43%, it does not make sense to use a flat rate based on weight.⁶
There may be a statistical average indicating which dosage is most likely to be appropriate for a given body weight. However, because individual variations are so great, each dosage must be determined on a case-by-case basis. Relying solely on a statistical average would constitute medical malpractice.

However, it has been reported that in cases of obesity, the maximum dose of 1 mg/kg is required more frequently.⁸¹

2.1.5.1.2. The optimal single dose may be lower than the lowest standard dose or higher than the upper limit of the standard dose range¶

Certain groups often require a lower target dose than usual. The following are frequently mentioned in this context:

• inattentive subtype
• concomitant ASA
• Adults often require lower doses than adolescents or children.

However, this does not rule out the possibility that people with ADHD in these groups may require very high doses.
In some cases, the optimal dose of MPH or AMP may be less than 5 mg per day. On the ADHD-Forum.adxs.org website, one person with ADHD reports that a single dose of 0.5 mg of Vyvanse provides the optimal effect.⁸²
Huberman reports a single case in which an optimal daily dose of 2.5 mg of Adderall was effective for a woman weighing 150 kg, and daily doses of 180 and 210 mg of Adderall were required for two sisters weighing 60 and 70 kg, respectively.³⁹ We, too, are aware of individual cases in which only extremely high doses of Vyvanse (several hundred mg per day and 50 mg as necessary sleep medication at night) achieved an adequate effect and significant improvement. One of these cases later turned out to be chronic poisoning from nitrogen oxides in the air or a particular sensitivity to them. Such high doses may only be administered under the close supervision of an experienced physician. We strongly caution against self-experimentation.

In the ADxS Drug Duration of Action Survey conducted by ADxS (as of Dec. 19, 23), 13% of 223 adult Vyvanse users reported an optimal dose below 30 mg, and 11.7% reported an optimal dose of 20 mg or less. 1.8% reported a dose of 10 mg or less. The 11.7% taking 20 mg or less had an average weight of 71 kg and an average age of 40 years.

The optimal dose may exceed the standard maximum dose (especially in rapid metabolizers). This applies to methylphenidate as well as to amphetamine-based medications.⁷⁷
For MPH, the standard maximum dose is 60 mg/day for children and adolescents and 80 mg/day for adults.
A maximum dose of 1 mg/kg of MPH is generally a good guideline for avoiding increased side effects. In some cases, however (when metabolism is correspondingly rapid), significantly higher doses are required and well tolerated.
Faraone and Biederman reported that, based on clinical experience, the typical dosage regimen for immediate release MPH in adults is 3 to 5 doses of 10 to 20 mg each. They specified 30 mg as the maximum single dose of MPH IR.⁸³

It is strongly advised not to mistake the first sign of improvement as an indication of an appropriate dose level, nor to treat arbitrary doses as target doses.⁸⁴ The dose should be persistently increased until two consecutive doses have resulted in a worsening of symptoms. It is not uncommon for a higher dose to have a worse effect than the next lower dose, while the dose one increment higher again produces a significant improvement.

2.1.5.1.3. Maximum dose¶

A maximum dose of 1 mg/kg of body weight, or 60 mg/day for children and 80 mg/day for adults, is often cited. However, there is no scientific evidence to support these maximum doses. These values are primarily cited by manufacturers, who naturally want to avoid potential risks in order to minimize liability risks.

As a rule of thumb, patients should not receive MPH doses exceeding 150 mg/day.⁸⁵⁸⁶

Hospital admission is indicated for children with a possible overdose at doses of 3 mg/kg or higher.⁸⁷ The laboratory warning level is 50 ng/ml.⁸⁸

It is evident that some people with ADHD require daily doses significantly higher than 60 or 80 mg. It is true that in these cases, more frequent monitoring is advisable. In any case, a blanket rejection of a dosage of up to 150 mg/day—which is necessary to achieve an adequate effect—is not justified.

A meta-analysis of k = 47 studies with n = 7,714 participants found that dosages exceeding the maximum daily doses recommended by the FDA⁸⁹

• For MPH, evidence of further improvement in symptoms (SMD 0.23) accompanied by a rapidly increasing risk of side effects
• In the case of AMP, there are no indications of further improvement in symptoms.

The results are averages and cannot be generalized to every patient. The authors conclude: “Clinicians may try doses above the recommended maximum doses if necessary and if tolerated, but should keep in mind that there may be no significant gains in response to the medication with these further dose increases.”

Further information is available from the health authorities in the respective regions:

• Europe: EMA: ema.europa.eu
  – United Kingdom: MHRA/BNF: bnf.nice.org.uk
• Australia: TGA: tga.gov.au
• Canada: Health Canada: canada.ca/en/health-canada → Drug Product Database
• Germany: Red List (Bertelsmann): fachinfo.de
• Austria: ages.at
• Switzerland: swissmedicinfo.ch

2.1.5.1.3.1. Maximum dose of methylphenidate¶

2.1.5.1.3.2. Maximum dose of amphetamine medications¶

2.1.5.1.3.3. Maximum dose of atomoxetine¶

2.1.5.1.3.4. Maximum dose of guanfacine¶

2.1.5.1.3.5. Maximum dose of clonidine¶

2.1.5.1.3.6. Maximum dose of bupropion¶

2.1.5.2. Target Factor 2: Full-Day Coverage / Number of Individual Doses¶

2.1.5.2.1. Full-Day Coverage as a Goal¶

The goal should be full-day coverage^{123137 138 139 140} , meaning coverage from 12 to 16 hours.¹⁴¹¹⁴⁰
The duration of medication coverage needed throughout the day is influenced by various factors.⁶
Here, a distinction must be made between:

• Symptoms related to attention and organization (medication as needed is acceptable, provided the person with ADHD prefers it)
  • Length of the school or work day
  • Demanding situations outside of work (events, social gatherings)
• Impulsivity and emotional dysregulation (requires 24/7 coverage; may be combined with ATX / guanfacine)
  • The need for medication to make social life more manageable

In any case, ADHD doesn’t end when school is over.

• Treatment should not be aimed solely at ensuring school readiness
• ADHD has a significant negative impact on homework, social life, and family life
• Untreated ADHD is associated with a significantly increased risk of accidents, which results in a reduction in life expectancy of 8 to 11 years (for more on this, see: Life expectancy reduced by 8 to 11 years In the chapter “Consequences of ADHD.” Failing to treat this condition cannot be objectively justified. An accident occurring during the part of the day when the individual is not on medication carries the risk of a liability claim. See the chapter Consequences of ADHD.

2.1.5.2.2. Number of single doses required for full-day coverage¶

The number of single doses of a suitable active ingredient and formulation required to provide coverage for a full day must be determined on an individual basis.⁷⁷ With MPH, the single-dose amount does not affect the duration of action of that single dose¹⁴², whereas with lisdexamfetamine, a higher single dose also prolongs the duration of action of that single dose.

If the daily intake is not met with a single dose of a medication:

• Multiple doses throughout the day (up to 3 doses of a half-day sustained-release formulation)
• Sustained-release formulations can also be supplemented with immediate release formulations
• Full-day coverage may require a combination of sustained-release and immediate-release stimulants.¹⁴³
• Dayana ER, a long-acting amphetamine formulation, is associated with a reduced need for additional doses of stimulants in immediate release¹⁴⁴

The concern that stimulant medications might interfere with sleep is rarely justified.⁶ As a rule, stimulants improve the quality of sleep for people with ADHD. For more information, see Treatment of Sleep Problems in ADHD

2.1.5.2.3. The duration of action of a single dose may be significantly shorter or longer¶

2.1.5.2.3.1. Manufacturer’s Specifications¶

Manufacturer’s specifications regarding duration of action (rarely achieved in practice)²⁵²⁶

• Immediate release MPH lasts 2.5–3.5 hours / single dose
  • 4 to 5 single doses are required for daily coverage
  • barely feasible in the long run, especially for children
  • For dosing, immediate-release MPH is still preferable because it allows for the most precise control
• Sustained-release MPH lasts an average of 5–6 hours per single dose
  • 2 doses + immediate-release MPH, if necessary, to cover the remainder¹⁴⁰
  • The second dose is usually 50% to 75% of the first dose
• Sustained-release MPH takes effect for an average of 10–12 hours
• Attentin (immediate release AMP) is effective for an average of 4.5 hours per single dose.³³
  • 2 doses and, if necessary, immediate-release MPH for residual coverage
  • The second dose is usually 50% to 75% of the first dose
• Lisdexamfetamine (Vyvanse) lasts for up to about 10–12 hours (Note: In practice, the duration is much shorter in more than 50% of people with ADHD!)
  • Amphetamine medications take 3 to 5 days to reach steady state
  • 1 dose and, if necessary, immediate-release MPH to cover the remainder
  • For rapid metabolizers (more than 50%—a second dose may be necessary)
  • For patients with a very fast metabolism, a third or fourth dose should also be considered
• Guanfacine
  • Mirror medication, once a day
• Atomoxetine
  • Mirror medication, once a day

2.1.5.2.3.2. Prolonged effect (rather rare)¶

It is rather rare for us to encounter people with ADHD who experience a significantly longer duration of effect from a single dose of an ADHD medication than what is specified by the manufacturer.
This is sometimes evident in the adequate effect of a given dose on the first and, if necessary, the second day of administration. On subsequent days, symptoms of overdose occur even when the dosage remains the same. In the case of amphetamine-based medications, the steady state should also be taken into account in this context due to the relatively long half-life.

2.1.5.2.3.3. Shortened duration of effect (fairly common)¶

In contrast, it is more common for people with ADHD to experience a single dose that lasts significantly shorter than the manufacturer specifies.
In our experience, about 15–20% of the people with ADHD are rapid metabolizers with a shorter duration of action for a single dose

• People with a fast metabolism often need several doses per day instead of higher single doses
• For about 50% of people with ADHD, the duration of action of stimulants is only 50% of what the manufacturer specifies
• mostly ultra-rapid metabolizers (rapid-metabolizing CYP or CES1 gene variant)
• multiple doses per day, including of extended-release formulations intended for all-day use
• Combination therapy for fine-tuning / in difficult cases
• in particular:
  • 50% ATX for full-day treatment of emotional dysregulation
  • 50% MPH or AMP, as they generally have a better effect on energy and concentration
• Rebound treatment
• Rebound is particularly common with MPH
• Solution:
  • Take the second dose in time so that its effects begin before the first dose wears off due to rebound
  • immediate release MPH shortly before the end of the last dose
    • 1/4 to 1/3 of what would be equivalent to a daily treatment dose
    • Example: 20 mg of half-day-release MPH is equivalent to 2 x 10 mg of immediate release MPH. In this case, take 2.5 to 3.5 mg of immediate release MPH 30 minutes before the end of the last sustained release dose.

The phenomenon of a shortened duration of action per single dose is significantly more common with Vyvanse than with MPH:

• Unlike with MPH, a significantly higher number of people with ADHD taking Vyvanse reported a significantly shorter duration of action than the 12 to 14 hours specified by the manufacturer. Many of them were able to achieve optimal daily coverage by taking several single doses. For more information, see Amphetamine-based medications for ADHD: Effect profile (over time) / Duration of action
• Some people with ADHD report that intense sports can shorten the duration of stimulants by up to 40%.¹⁴⁶
• Higher doses of amphetamine have a longer-lasting effect in a person⁶
  • Since amphetamine is excreted by the kidneys, renal blood flow—in addition to the total dose—plays a small but measurable role in the duration of action
  • Another consequence of this is that blood levels of amphetamine change more slowly and are less prone to rebound than with methylphenidate

2.1.5.2.4. Information on the duration of action of the prescribed doses¶

When administering a single dose, people with ADHD must be explicitly informed of the typical duration of action of a single dose of the respective medication. This is not only ethically required, but also medically and therapeutically necessary.
We repeatedly receive reports from people with ADHD who were led to believe that a single dose of immediate release or half-day extended-release MPH (e.g., Ritalin for adults) would last all day, rather than being informed of the usual duration of action of 2.5–3 hours (immediate release) or 5–6 hours (half-day extended-release). This naturally leads to inaccurate feedback to the doctor when patients report that their symptoms remain unchanged, because—unaware of the limited duration of action—they mistakenly describe the period in the afternoon or evening when the medication is no longer effective.

2.1.6. Dosage Adjustments¶

• The perception that a very positive effect experienced after the initial adjustment wears off after a few days or weeks is often not due to a change in the effect itself, but rather to a change in the perception of people with ADHD. During the so-called “honeymoon phase” immediately after reaching an effective dose, the contrast with the previous state of deficiency is perceived as a particularly positive experience. Such a feeling of marked improvement is, by its very nature, fleeting—just as the euphoria a soccer fan feels after winning a championship returns to normal within days, even though they’ve been on the edge of their seat all season. In such cases, it’s important to carefully assess whether a higher dose is truly necessary. External assessments can be helpful in this regard.
• It is possible that a one-time readjustment may be necessary after a few months. This is not a result of the body getting used to the device.
• A trial of discontinuing medication should be conducted once a year to determine whether ADHD symptoms persist without medication.
• People with ADHD frequently exhibit 75% of the possible ADHD symptoms, while persons with ADHD exhibit 12 to 25%. The goal of optimal dosing is therefore not complete freedom from symptoms, but rather a reduction of symptoms to a healthy level. Attempting to increase the dosage until all symptoms are completely eliminated would inevitably result in an overdose.

2.1.7. Intake Based on Need¶

The greater a person with ADHD’s ability to self-manage, the more likely they are to take stimulants as needed. While a rigid dosing schedule is generally the safer approach for children, once the initial titration phase is complete, adults are more likely to decide on a day-by-day basis whether and at what dose to take their prescribed stimulants (within the dosing range agreed upon with their doctor). Some people with ADHD can manage this well when specific tasks (e.g., evening events) require an additional evening dose or the sole dose on an otherwise medication-free (because it’s a low-demand) weekend day (such as shopping on Saturday afternoon or while on vacation). The guiding principle is “I manage my ADHD; my ADHD doesn’t manage me.” ⁸¹
During the titration phase, adults must not deviate from the prescribed regimen. We repeatedly observe that the impulsivity and impatience of people with ADHD lead them to change the dose or the timing of administration within 2 or 3 days. However, this is primarily a symptom of the disorder. Stimulants require several days of consistent dosing to enable a stable sense of self.
For women, the days leading up to menstruation are often associated with an increased need for stimulants. For more information, see the section below at Cycle-related symptom fluctuations in women.

2.1.8. Metabolism of Drugs and Active Ingredients¶

A change in medication or active ingredient may be necessary or helpful due to adverse side effects or lack of response (no effect).

If a medication has no effect (non-response), the first step—especially with MPH—should be to switch to a different MPH formulation. Surprisingly often, people with ADHD react negatively to one MPH formulation or experience severe side effects from it, yet respond positively to another MPH formulation, while others may experience the exact opposite. A large study found that 85% of people with ADHD switched formulations.¹⁴⁷

If an active ingredient shows no effect overall (regardless of the formulation) (non-responsive), another active ingredient should be tried first.
About 30% of all people with ADHD do not respond to MPH, and about 20% do not respond to AMP (nonresponders). However, nonresponse rarely affects both active ingredients at the same time, so that about 85% to 90% of people with ADHD respond to either MPH or AMP. 40% to 50% of MPH nonresponders respond to atomoxetine.

When switching between methylphenidate and amphetamine-based medications, no medication-free interval is required due to their short half-life. Similarly, no adverse effects have been reported with ADHD medications such as guanfacine or atomoxetine when switching between them in a timely manner. When switching from MAO inhibitors to stimulants or atomoxetine, or from stimulants or atomoxetine to an MAO inhibitor, a 14-day waiting period must be observed—and, of course, concurrent use is not permitted.

It has been reported that the optimal dose of stimulants—which is often highly individualized—may vary between MPH and AMP. A person with ADHD may require a relatively high dose of MPH or a relatively low dose of AMP to achieve an adequate effect. Therefore, when switching active ingredients, individual titration must be repeated.⁸¹ As a consequence, the standard conversion tables should be viewed with caution when switching active ingredients.

2.1.8.1. Non-responders: Drug Metabolism¶

• MPH: 30% non-responders
  • If MPH is ineffective:
    • Check stomach acid levels
    • Change the active ingredient
• AMP: 20% non-responders
  • If AMP is ineffective:
    • Check the pH level of your urine at the time of administration

For more than 40% of people with ADHD who do not respond to treatment, switching medications within the first 3 months is helpful.¹⁴⁸
When switching between MPH and AMP due to nonresponse, only about 10%³³ to 15% remain who are nonresponders to both types of stimulants.²⁵²⁶ This is, after all, 1.6 to 2.5 times the rate of purely random double non-responsiveness (30% x 20% = 6%), which suggests that there are indeed common factors influencing responsiveness, even if they are few.

REVIEW of Treatment Options for Treatment-Resistant ADHD: Cortese et al.¹⁴⁹

• Optimize stimulants
• Try alternative monotherapies
• Try non-stimulants
• combination drug therapy
  • A combination of stimulants and non-stimulants is superior to monotherapy with only one class of active ingredients
• Use off-label medications that have been shown to help with ADHD
• treat comorbid conditions

2.1.8.2. Side Effects: Drug-Drug or Drug-Active Ingredient Interactions¶

To avoid side effects, see the section below titled “Avoiding Side Effects.”

• MPH
  • in case of severe side effects:
    • Check: Have the recommendations under “Avoiding Side Effects” been followed, especially regarding completely avoiding caffeine?
    • Overdose?
    • Do you need a very low dosage?
    • in cases where MPH generally responds:
      • : Change your medication first
        • surprisingly varied side effects
          • Person A cannot tolerate drug A but tolerates drug B just fine; Person B is exactly the opposite: it’s unpredictable
        • Alternative products, e.g.:
          • immediate release
          • Medikinet Retard / Adult
          • Ritalin LA / Adult
          • Concerta
          • Kinecteen
      • then switch to a different active ingredient
        • For recommended order of use, see above under “Medication Selection”
• AMP
  • in case of severe side effects:
    • Check: Have the recommendations under “Avoiding Side Effects” been followed, especially regarding completely avoiding caffeine?
    • Overdose?
    • Do you need a very low dosage?
    • when AMP responds in general:
      • : Change your medication first
        • surprisingly varied side effects
          • Person A cannot tolerate drug A but tolerates drug B just fine; Person B is exactly the opposite: it’s unpredictable
        • Alternative products, e.g.:
          • Lisdexamfetamine (Vyvanse)
          • immediate release (Attentin)
          • Amphetamine solution (to be prepared by a pharmacy)
          • United States: a large number of additional approved drugs
      • then switch to a different active ingredient
        • For recommended order of use, see above under “Medication Selection”

2.1.8.3. Conversion Tables for Switching Between Stimulants¶

A conversion table from dexamphetamine to Vyvanse can be found on ADHSpedia.¹⁵⁰

When switching medications or active ingredients due to side effects, the conversion table by Kühle is very helpful (in German). It provides a guide to which dose of a different type of stimulant corresponds to the dose of the medication previously taken. The UpToDate conversion table (in English) is also helpful.¹⁵¹

A comprehensive conversion table for American stimulant medications, including recommendations for the transition process, can be found in Stutzman et al.³¹

2.1.9. Development of Tolerance to Stimulants / Habituation Effects¶

For more details, see ⇒ Medications: Development of Tolerance

2.1.10. Withdrawal from Stimulants¶

Stimulants such as methylphenidate or amphetamine-based medications have an immediate, dose-dependent effect. As a general rule, they can be discontinued immediately and without side effects. Compared to the—sometimes very severe—side effects that people with ADHD repeatedly report from discontinuing antidepressants—especially when done too quickly—it can generally be said that stimulants do not cause any withdrawal issues. However, people with ADHD then suffer from a recurrence of ADHD symptoms, which can subjectively be misinterpreted as a withdrawal side effect.
However, there are reports from people with ADHD who have experienced withdrawal symptoms associated with amphetamine-based medications, in some cases lasting up to 14 days. For a minority of these people, these symptoms appear to go beyond the unpleasant experience of a recurrence of ADHD symptoms. If necessary, this could be addressed by tapering off the medication gradually.
We have received a report of withdrawal symptoms in a single case following discontinuation of a 10-fold overdose of Vyvanse (50 mg; the patient required only 5 mg).

2.1.11. Medication Adherence¶

Although ADHD medications do not cure the condition, most people with ADHD do not take medication for the rest of their lives or take breaks from medication lasting more than 12 months.
This may indicate fluctuating ADHD. For more information, see Fluctuating ADHD in the article “ : ADHD in Adults”.

Of n = 198 children and adolescents between the ages of 6 and 18 (mean age 10.7 years), 33.9% had at least partially discontinued their ADHD medication after 6 months. Older age and a lower IQ were associated with nonadherence. Neither monotherapy versus combination therapy nor the use of stimulants versus non-stimulants predicted discontinuation of medication.¹⁵²
Among Finnish children and adolescents with ADHD, the median duration of medication use (until discontinuation for at least 12 months) was 3.2 years. Boys had a longer duration of treatment than girls, and the younger the participants were, the longer the duration of treatment. Boys aged 6 to 8 had the longest duration of treatment, with a median of 6.3 years.¹⁵³
Of n = 7,661 people with ADHD, with an average age of 21.8 years, only 55.4% were prescribed medication. Of the n = 4,011 people with ADHD for whom information on medication adherence was available, the average adherence rate was 56%. 27.5% took their medication on at least 80% of the days over a 2-year period.¹⁵⁴

2.2. Dosing with immediate release MPH¶

Immediate-release MPH, on the one hand, allows for better monitoring of symptom improvement; on the other hand, it requires more reliable patient compliance due to the higher number of single doses per day. Therefore, a single daily dose of sustained-release medication may be recommended for children, and especially for younger children.

According to the 2018 German S3 guideline, immediate release MPH may be considered for the following reasons, for example:¹⁵⁵
• More precise dose adjustment during the initial titration phase of the medication
• the need for greater flexibility in dosing regimens

Based on our experience, we recommend the following:

• Start with a single, very low dose (2.5 mg of immediate release MPH) and, for the time being, make a conscious effort not to expect any effects at all.
  • Since half-day-release MPH is available in doses starting at 5 mg, a single 5-mg dose of sustained-release MPH can be taken instead of two doses of immediate release MPH (typical duration of action: approximately 5–6 hours)
• After 4 to 7 days, 2.5 mg (immediate release) twice daily
• Continue to increase the number of single doses every 4 to 7 days until the entire day is covered.
  Immediate-release MPH lasts only 2.5 to 3 hours, 3 to 5 single doses are required to cover the entire day. With only two doses, almost the entire day would go without medication. This could completely distort the assessment made by people with ADHD or by third parties, especially if they have not been informed about the limited duration of action (and the expected rebound effect). Above all, however, it would not sufficiently alleviate the symptoms and thus the burden on the person with ADHD.
• Increase single doses to 5 mg (sustained release to 10 mg per single dose)
  • When doing so, increase only a single dose at a time, starting with the first dose (e.g., 2.5 / 2.5 / 2.5 to 5 / 2.5 / 2.5 to 5 / 5 / 2.5, etc.)
• After that, increase the dose by a maximum of 2.5 mg per single dose of immediate release MPH every 4 to 7 days.
  We consider dose increments of 5 mg of immediate release MPH per single dose (or 10 mg per single dose of half-day extended-release MPH, as recommended, for example, in the Medikinet prescribing information) to be detrimental.
  • Purpose: Gradually increasing the dose prevents the optimal dose from being missed.
    In our experience, while not many, a significant proportion of people with ADHD have a very narrow window for optimal dosing—well below 5 mg—such that 2.5 mg less per single dose is insufficient, and 2.5 mg more can already trigger the first signs of an overdose. Similarly: Dreher.⁴¹ It is likely that cases have frequently been attributed to intolerance when, in reality, they were due to inappropriate dosages.
    Since such fine-grained dosing increments do not harm other people with ADHD (but, on the contrary, help prevent dosage-related side effects),¹⁵⁶ dosing increments in 2.5-mg increments (based on a single immediate-release dose of MPH) should be the gold standard. Kühle agrees.¹⁵⁷ A large meta-analysis points in the same direction.⁷³
    Other sources recommend starting with 1–2 single doses of 5 mg and increasing the single dose weekly in 5-mg increments.¹⁵⁸ For the reasons mentioned, we consider these dose increments to be too large.
    For people with ADHD, for whom even extremely small differences in dosage are critical, a pharmacy in Switzerland offers MPH drops. One drop contains 0.35 mg of MPH. It is manufactured in batches and preserved with E216 and E218.¹⁵⁹ One person with ADHD reports that dissolving immediate-release MPH in alcohol in such precise amounts that they could be measured drop by drop yielded a comparable result.
• Inform people with ADHD and (informed) third-party observers about
  • The typical duration of action of the respective medication
  • The option of a shorter or longer duration of action, depending on individual needs
  • On the expected rebound
    Knowing the typical duration of action—and that this can vary from person to person—is just as important for monitoring the effect and its end as it is for ensuring that the last dose is taken well enough in advance of bedtime so that the effect has worn off at least one hour beforehand. For some people with ADHD (we suspect this is more common in ADHD-I than in ADHD-HI), a reduced dose (1/5 to 1/2 of an optimized single dose) in an immediate release form may help them fall asleep. The same principle applies here: Test very low doses (1/10 of the single daily dose) when using the medication as a sleep aid. When doing so, convert sustained-release daily doses to their equivalent immediate release duration of action. (Example: 20 mg sustained release with a duration of action of 5–6 hours corresponds to 10 mg immediate release with a duration of action of 2.5–3 hours).
• Increase the dosage until a very satisfactory effect is achieved.
  • For most, but not all, people with ADHD, a higher dose results in greater symptom relief.¹⁶⁰
• When taking a daily dose of 20, 40, or 60 mg of MPH, a follow-up consultation with the treating physician should be scheduled in each case.
• It is also recommended that you keep a diary (see below). Some doctors expect you to submit your diary weekly, for example, by email. This can help identify any adverse developments early on.
• After reaching what is believed to be the optimal dose, increase the dose two more times to determine whether any adverse symptoms now appear.
  Purpose:
  This ensures that not only are symptoms improved, but the optimal dose is also determined. Furthermore, the person with ADHD learns what it feels like when the dosage is slightly too high. This is important so that the person with ADHD can develop a sense of what the optimal dosage is and, if necessary, suggest further dose reductions.
• It is possible that side effects may occur at certain dosage levels below the optimal dose, which then disappear again at higher dosage levels. In particular, internal tremors (like having one too many cups of coffee) may subside within 2 to 3 days after a dose increase. This may be due to the noradrenergic system adjusting. Several people with ADHD have reported to us that this internal trembling no longer occurred at the next or subsequent dosage level. If it becomes more pronounced or persists, it is a sign of overdose.
• “Zombie-like” symptoms may indicate either an overdose or an underlying depression that has come to the surface.
  • Stimulants block sensory filters: This is likely one of the reasons why students may “try out” stimulants during stressful exam periods (which we strongly advise against), but then stop taking them on their own initiative afterward. In fact, students who misuse stimulants during exam periods exhibit an above-average number of ADHD symptoms.¹⁶¹
  • People (other than people with ADHD) whose sensory filters are not overly open experience a reduced quality of life as a result. There are no reports of students voluntarily taking MPH outside of very stressful exam periods (unless they have severe ADHD symptoms¹⁶² )
  • Stimulants inhibit the limbic system. An overdose can therefore diminish emotional sensitivity.¹⁶³
• The manufacturer’s information on the typical duration of action applies only to individuals with standard variants of the metabolism-related genes. However, many people with ADHD have variations in the relevant metabolism gene (MPH: CES1 gene; AMP, atomoxetine, bupropion: CYP2D6 gene; guanfacine: CYP3A4 gene). In addition to CYP 450 enzymes, there are genetic variants of the POR gene that, in turn, influence the efficacy of the CYP enzymes, meaning that the CYP genetic variant alone is not sufficient to draw conclusions. For more information, see CYP2D6 Metabolizing Enzyme, CYP3A4 Metabolizing Enzyme, CES1 Metabolizing Enzyme. In addition, there are other pharmacological factors that influence the duration of action. For more information, see Effects and Duration of Action of ADHD Medications
• Variations are so common that the typical duration of action cannot be assumed. It must be assessed individually for each person with ADHD.
  • A single dose of Vyvanse lasts for only 5 to 7 hours at most in two-thirds of the people with ADHD. The typical duration of 12 hours specified by the manufacturer is therefore far from being achieved by the majority of the people with ADHD.
  • In almost all metabolizers (approximately 15 to 20% of people with ADHD), immediate-release MPH lasts only about 1 to 1.25 hours instead of the usual 2.5 to 3 hours, Medikinet or Ritalin for adults for only about 3 hours instead of the usual 5 to 6 hours, and Vyvanse for 5 to 7 hours instead of the usual 10 to 12 hours. The rapid metabolizers known to us reported that they tolerated correspondingly more frequent dosing and correspondingly higher daily doses well, without any side effects. Nevertheless, given the required increase in the number of doses per day and the resulting potential for exceeding the general maximum dosage recommendations, closer monitoring is certainly necessary.
  • If metabolism occurs too rapidly, this can sometimes be counteracted by cross-inhibition with inhibitors of the relevant metabolic enzyme. For example, several people with ADHD for whom Vyvanse (which is metabolized via CYP2D6) had a much too short duration of action or no effect at all reported a satisfactory effect and duration of action after combining it with bupropion, which reduces CYP2D6 expression.

2.3. Transition to sustained-release MPH / AMP¶

Once treatment with immediate release MPH has been initiated, the number of daily doses should be reduced by using extended-release formulations, since the 4 to 6 daily doses of immediate release MPH that would otherwise be required¹⁶⁴ are barely possible for children and adolescents to maintain. Medication adherence decreases in proportion to the required frequency of dosing.¹⁶⁵ Since people with ADHD are notoriously disorganized and forgetful, each additional dose presents another opportunity to forget to take the medication. Furthermore, the embarrassment and teasing that adolescents experience when they have to pick up their medication from the school nurse are among the most common reasons for discontinuing medication treatment.⁶ A single daily dose improves compliance.¹⁶⁶
Immediate release MPH is not approved for adults in Germany and can only be prescribed off-label.

Whether immediate release or sustained-release MPH works better varies from person to person. In a 1-year study, about half of the people with ADHD preferred immediate release MPH, while the other half preferred OROS MPH.¹⁶⁷ As a rule, people with ADHD are better able to assess which type of medication works best for them than their doctor. Therefore, the person with ADHD’s experience should be taken into account.

With sustained-release MPH, pharmacological methods are used to release several doses in succession.
Due to significant individual differences in duration of action, it is possible (albeit rare) that the first dose will be metabolized so quickly that a gap in efficacy occurs before the second dose takes effect. This can be avoided by taking several (possibly reduced) doses at staggered intervals. For example, if 20 mg of sustained-release MPH has an action profile of 2 hours of effect + 30 minutes of treatment gap + 2 hours of effect, one option would be to administer two 10-mg sustained-release doses 30 minutes apart.

For people who have difficulty eating in the morning, Medikinet Adult and Medikinet Retard are not suitable, as these medications only provide their sustained release effect when taken with food. In such cases, Ritalin Adult, Ritalin LA, or an OROS formulation such as Concerta should be considered.

2.4. AMP Dosage¶

In addition to the general information provided above regarding the administration of stimulants and determining the appropriate starting dose, the following applies:

2.4.1. Lisdexamfetamine (Vyvanse, Tyvanse)¶

The manufacturer’s recommended starting dose of 30 mg for lisdexamfetamine was not determined in clinical trials. The manufacturer has not conducted any studies with starting doses lower than 30 mg. The setting of the starting dose at 30 mg is therefore based solely on regulatory considerations. It is not supported by any pharmacological studies.

• Since amphetamine-based medications are the first choice of medication for adults (offering the greatest effect size and fewest side effects among all ADHD medications), it would make sense to start treatment directly with these medications.
• Vyvanse/Tyvanse contains lisdexamfetamine dimesylate. Lisdexamfetamine dimesylate is dextroamphetamine base bound to lysine. The lysine bond results in a slower and more gradual release of dextroamphetamine into the bloodstream, thereby providing a prolonged effect compared to dextroamphetamine sulfate medications.
  The following are available in the U.S.:
  Capsules: 10, 20, 30, 40, 50, 60, 70 mg
  Chewable tablets: 10, 20, 30, 40, 50, 60 mg
• In our experience, the 30 mg dose recommended as the standard initial dose carries a significant risk of overdose and increases the risk of side effects associated with the initial dose.
  • We know of quite a few adults with ADHD for whom the optimal dosage range for Vyvanse falls within a margin of less than 5 mg per single dose. 5 mg less is too little; 5 mg more is an overdose. We also know of a few adult people with ADHD for whom 3 mg of Vyvanse per day is the optimal dose. Therefore—contrary to the majority opinion—we would consider dosing increments of 5 mg of LDX dimethylate to be more appropriate than the officially recommended 10 mg increments. See also the section above on titration of immediate release MPH.
  • There are also people with ADHD who experience side effects with lower doses of LDX that disappear at higher doses. It is unknown whether these are general side effects associated with the dose—which would have occurred for a limited time even at higher doses—or side effects specific to low doses.
  • Starting with lower doses therefore has both advantages and disadvantages.
    • It requires more persistence when measuring out the dosage
    • It reduces the risk of side effects from an overdose
    • It increases the risk of side effects associated with underdosing
    • With sufficient persistence and patience, it increases the chances of finding the right dose for each individual
    • For people with anxiety, it is often difficult to muster this kind of perseverance and patience. In such cases, it is generally recommended to start with the standard initial dose of 30 mg.
    • In any case, the decision of the attending physician is decisive
  • In 2002, the American Academy of Child and Adolescent Psychiatry (AACAP) recommended a starting dose of 2.5 mg of dextroamphetamine or mixed amphetamine salts, in immediate release form, taken 2 to 3 times daily.¹⁵

Lisdexamfetamine dimesylate (capsule, e.g., Vyvanse)	Dextroamphetamine sulfate (tablet, e.g., Attentin)	Dextroamphetamine base (pharmacologically active)	Lisdexamfetamine base (irrelevant)
10 mg		2.95 mg	5.78 mg
	5 mg	3.67 mg
20 mg	8.04 mg	5.90 mg	11.56 mg
	10 mg	7.39 mg
30 mg	12.06 mg	8.85 mg	17.34 mg
40 mg	16.08 mg	11.80 mg	23.12 mg
	20 mg	14.68 mg
50 mg	20.10 mg	14.75 mg	28.90 mg
60 mg	24.12 mg	17.70 mg	34.68 mg
70 mg	28.14 mg	20.65 mg	40.46 mg
	30 mg	22.01 mg
	40 mg	29.35 mg

The conversion ratio of lisdexamfetamine dimesylate (LDX capsules) to pharmacologically active dextroamphetamine base is 0.2948.¹⁶⁸
The conversion factor for dextroamphetamine sulfate (Attentin tablets) to dextroamphetamine base can be set at 0.7338.¹⁶⁹
Lisdexamfetamine base is listed for informational purposes only.

• In a study of 4- to 5-year-old children with ADHD, in which treatment began with a dose of 5 mg of LDX and was increased by 5 mg of LDX each week, the optimal dose was:¹⁷⁰
  • 5 mg at 5.2%
  • 10 mg at 36.8%
  • 15 mg at 31.6%
  • 20 mg at 10.5%
  • 30 mg at 47.4%
  • The mean daily dose of LDX in Week 8 was 22.9 mg/day (SD 7.25 mg).
• In a subsequent Phase III study involving N = 199 preschool children treated with fixed doses of lisdexamfetamine dimelsial ranging from 5 to 30 mg, there was also no evidence of disadvantages associated with a low dose or advantages associated with a higher dose. Rather, the dose-response relationship is highly individualized.¹⁷¹
• Although the Vyvanse package insert does not permit dividing the capsule contents, based on many years of experience among a large number of people with ADHD, this is a practical approach for both administering the medication and determining the optimal dose. We are not aware of any reports of fluctuations in efficacy due to uneven distribution of the active ingredient. Precise dosing can be achieved—to within a milligram—by dissolving the capsule contents in water and dividing the solution using a syringe. This is also noted by Kühle in the equivalence table.²⁹ A slightly less precise method involves dividing the capsules into equal-sized piles using a razor blade on a glass surface.
• Vyvanse dissolved in water will keep in the refrigerator for a few days. Small mounds of Vyvanse spread out on a dry glass plate will keep at room temperature for several days. You can further extend the shelf life by covering them airtight with plastic wrap. However, this is generally not necessary. Always keep the product out of the reach of children.
• Due to its long half-life, Vyvanse can take up to 5 days to reach steady state.⁷⁶ After a break in treatment, unpleasant side effects may occur during the first few days, but these usually subside quickly.

This video explains how to split Vyvanse capsules into small doses.

2.4.2. Adderall N (immediate release)¶

The FDA recommends the following single dose of immediate release amphetamine salts (Adderall) for ADHD:¹⁷²¹⁷³
- Children under 3 years of age: Amphetamine is not recommended
- Children ages 3 to 5:
- immediate release AMP
- Starting dose of 2.5 mg once daily in the morning after waking up
- Subsequent doses at 4- to 6-hour intervals
- weekly increase in 2.5 mg increments until the optimal response is achieved
- Dosage range of 2.5 to 40 mg per day, divided into 1 to 3 doses
- Children 6 years of age and older
- immediate release AMP
- Initial dose of 5 mg once or twice daily at 4- to 6-hour intervals
- weekly increase in 5-mg increments until the optimal response is achieved
- Dosage range of 5 to 40 mg per day, divided into 1 to 3 doses
- sustained release AMP
- Initial dose of 5 to 10 mg once daily in the morning
- Weekly increases in increments of 5 to 10 mg until the optimal response is achieved
- Maximum daily dose: 30 mg per day
- Teens
- immediate release AMP
- Initial dose of 5 mg once or twice daily at 4- to 6-hour intervals
- weekly increase in 5-mg increments until the optimal response is achieved
- Dosage range of 5 to 40 mg per day, divided into 1 to 3 doses
- sustained release AMP
- Starting dose of 10 mg once daily in the morning
- weekly increase in 10-mg increments until the optimal response is achieved
- Insufficient evidence of better results at doses higher than 20 mg per day
- Note: This does not correspond to the experiences with Vyvanse in Europe
- Adults
- immediate release AMP
- Initial dose of 5 mg once or twice daily at 4- to 6-hour intervals
- weekly increase in 5-mg increments until the optimal response is achieved
- Dosage range of 5 to 40 mg per day, divided into 1 to 3 doses
- sustained release AMP
- Starting dose of 20 mg once daily in the morning
- Insufficient evidence of better results at doses higher than 20 mg per day

3. Dosage of Non-Stimulants¶

Non-stimulants are the third-line treatment for ADHD, after the stimulants AMP and MPH.
Clinicians report that non-stimulants sometimes lose their effectiveness after 9 to 18 months, at which point it becomes necessary to switch to another non-stimulant.⁶ There are no studies with observation periods of that length.

3.1. Dosage of Atomoxetine¶

According to the available research⁷⁵ as well as our own experience, gradual up-dosing also has the advantage of reducing the incidence of side effects with atomoxetine. While a study supported by the manufacturer does not provide a clear picture¹⁷⁴, other studies report that patients are less likely to discontinue treatment due to side effects when the dose is increased gradually, even though the incidence of side effects was comparable.¹⁷⁵
In some cases, it is recommended to start with a dose of 10 mg for women or 18 mg for men, increasing the dose every 14 days⁸¹, rather than with 40 mg/day, or to begin with an initial dose of 18 to 25 mg.³⁵
Atomoxetine is available as non-divisible capsules and as divisible tablets.

For long-term use, the recommended daily dose is 1.2 mg/kg, and the maximum daily dose is 100 mg.⁸¹
ATX is usually taken in the morning. If drowsiness is a side effect, ATX can also be taken in the evening.³⁵
According to the prescribing information for Strattera, if people with ADHD experience side effects with a single daily dose of atomoxetine, the dose may be split into two half-doses, one in the morning and one in the evening.¹⁷⁶

The first effects may become noticeable after 2 to 3 days. It takes 8 to 10 weeks for atomoxetine to reach its full effect.⁶

Unlike with stimulants, it is important to take atomoxetine consistently.⁸¹

In our opinion, when tapering off the medication—as with all antidepressant-like drugs—a gradual approach is highly recommended. A different view is presented by Prasad et al.⁷⁵ However, we have received several reports of depression as a side effect of rapid discontinuation of atomoxetine.

Since atomoxetine can increase blood pressure and heart rate, these should be monitored.⁶

3.2. Dosage of Guanfacin¶

Guanfacine appears to reduce norepinephrine levels during the first 2 weeks of treatment. Only after that does norepinephrine appear to increase as a result of receptor downregulation.
The consequences are that—as with antidepressants—it takes several weeks for the effects to become apparent.¹⁷⁷

Because of guanfacine’s blood pressure-lowering effect, it must be tapered off gradually when discontinuing treatment to avoid blood pressure problems.⁸⁴

3.3. Dosage of additional non-stimulants¶

With other non-stimulant medications, such as bupropion, imipramine, or desipramine, it can also take 8 to 10 weeks for the full effect to set in.⁶

When starting treatment with THC-containing medications, an initial dose of 1 to 2.5 mg of THC per day is recommended. The dose should be increased gradually, by 1 to 2.5 mg every 3 to 5 days. The average daily dose is 10 to 20 mg of THC.¹⁷⁸

3.4. Serotonin reuptake inhibitors¶

The use of serotonin reuptake inhibitors should always be discussed with a doctor on an individual basis. Serotonin reuptake inhibitors are suitable for the treatment of (comorbid) depression.
With regard to ADHD, treatment with minimal doses (e.g., 2 to 5 mg of escitalopram) might be useful for addressing impulsivity in ADHD-HI; in our experience, this appears to have an immediate effect and is apparently not mediated by receptor down- or upregulation.
Furthermore, serotonergic medications are not appropriate for treating ADHD itself, and in particular for ADHD-I.

3.5. Taper off blood pressure medication gradually¶

Medications used to regulate blood sugar levels must be introduced gradually and tapered off gradually.
With serotonin reuptake inhibitors, this can take more than half a year to avoid side effects.

4. Monitor and document dosing¶

4.1. Self-monitoring: Keep a dosing diary (e.g., ADxS dosing guide)¶

Download the ADxS Dosage Guide: ⇒ Dosage Guide in the ADHD Forum on ADxS.org

During the initial dosing period, you should keep a diary that records how you feel each day. It should include:

• Daily assessment for each relevant symptom
  • Identify individual symptoms using the complete list of symptoms: ⇒ Complete list of ADHD symptoms by presentation
• Preparation
  • Not just an active ingredient
  • For generic drugs, also the manufacturer
• Dose
• Time(s) to take
• Other medications taken (type, dose, time(s))
• Food and Fluid Intake (Type, Amount)
• Nicotine consumption (Always completely avoid coffee when titrating ADHD medication doses)
• Menstrual Cycle in Girls and Women
  For more information, visit ⇒ Gender Differences in ADHD
• Sports
• Specific stressors (both emotional and physical, e.g., arguments, illnesses, allergies, etc.)

Important: The effectiveness of the medication and the dosage should never be assessed based on individual days, but always retrospectively, using an average over 3 to 4 days. Otherwise, irrelevant and random correlations will be overemphasized.

4.2. Observation by Others¶

Since not all people with ADHD are able to perceive the actual positive effects themselves in a timely manner (comorbid autistic traits, in particular, can make this difficult), supplementary observation by others is advisable.

Observation by a third party should be conducted by a family member or partner who is familiar with the situation and should also be documented using a dosing diary, such as the ADxS dosing guide.

In addition, it is helpful to discreetly ask third parties who are not aware of the medication regimen about any changes they may have noticed.
Such feedback is particularly valuable and meaningful when these third parties are unaware that medication is being taken. Otherwise, these third parties’ attitudes toward and expectations of medication would subconsciously influence their assessment and alter the results.
To avoid bias in the assessment of the drug’s effects by teachers or other caregivers, it is therefore advisable not to inform them of the medication use at first. If they nevertheless report a significant change in behavior within the first few weeks, this unbiased observation is much more meaningful.

The combination of ongoing observation by a family member in the know (who, ideally, knows only about the medication itself but nothing about dose changes, changes in active ingredients, or missed doses) and impartial third parties—who are also unaware of the fact that the patient is taking medication at all—can provide very valuable insights into the medication’s effects.

Reports are only meaningful if the medication’s duration of action is long enough. A single immediate-release MPH tablet taken in the morning cannot produce changes that last beyond its 2.5- to 4-hour duration of action.

With younger children, it can be very helpful not to tell them directly that they are now taking medication, but rather to refer to it as vitamins during the initial dosing phase. After a few weeks, talking with their teachers—who are also not in on the secret—can provide insight into whether they have noticed these changes.

4.3. Measuring the Effectiveness of Medication¶

Various attempts to adjust medication dosages for ADHD based on blood test results have so far shown little success.
With regard to ATX, it was reported that blood level measurements did not yield any useful values.
Since stimulants are known to require dosing that is not weight-dependent, and since the doses required to achieve an appropriate effect vary greatly from person to person, we find it difficult to see the potential benefit of measuring blood levels.

Some physicians use sustained attention tests to identify intra-individual differences without medication and at various medication doses, and to monitor responding and the effects of stimulants. Since attention tests depend heavily on the individual participant’s motivation and, in cases of high intrinsic motivation to participate, can falsely convey the impression that a person is unaffected even in cases of severe ADHD, such tests should not be used as the sole criterion. However, using them as a supplementary assessment tool—particularly in a trained and consistently controlled (boring) testing environment—can be helpful.

A meta-analysis reports promising results from the Qb-Test in measuring the effectiveness of medication for ADHD.¹⁷⁹
The Qb test measures the subject’s facial expressions while they complete a Go/NoGo test. It remains to be seen whether the results are consistent enough to assess individual cases. Furthermore, the time required to administer the test is likely to prevent its widespread use in medical practice.

4.4. Monitoring Medication Adherence¶

It is a common myth that ADHD medications—especially stimulants—can be addictive. If that were the case, there wouldn’t be a problem with people with ADHD forgetting to take their medication.
The use of a medication reminder app drastically improved medication adherence (medication refill interval: 46 days without the app, 34 days with the app).¹⁸⁰

5. Avoiding Side Effects¶

At the dose that provides optimal symptom relief for each individual (which may be significantly lower than typical doses!), very few people with ADHD experience side effects. The most common side effects are

• Dry mouth (a few days)
• mild, temporary loss of appetite

Side effects and effect size must be weighed against one another.
To achieve a 1 percentage point lower risk of side effects, adults with ADHD were willing to forgo percentage points of improvement in ADHD symptoms:¹⁸¹
0.59 Nausea (a 1 percentage point reduction in nausea was equivalent to a 0.59 percentage point worsening of ADHD symptoms)
0.57 Insomnia
0.49 Anxiety
0.32 Nervousness
0.17 Dry mouth

Rare, more serious side effects (high blood pressure, aggression, or others) should be discussed with your doctor immediately.

5.1. A particular challenge: Dosage adjustment in cases of comorbid anxiety¶

In our experience, people with ADHD or high anxiety scores often experience more severe side effects.
For more information, see Treatment Guidelines for Specific Comorbidities: ADHD and Anxiety In the article “Guidelines for ADHD Treatment.”

5.2. No caffeine when taking stimulants (IMPORTANT!)¶

When titrating the dose of stimulants, caffeine should be completely eliminated without exception.
Since the side effects of caffeine and stimulants can be cumulative¹⁸², consuming them together may cause side effects that do not occur when caffeine or stimulants are taken alone.
Therefore, caffeine must be completely and consistently avoided when taking stimulants. This may be subjectively difficult for people with ADHD who previously managed their symptoms with high caffeine intake. However, the role of reducing symptoms is now (and much more effectively) fulfilled by the stimulants.
In addition to the overdose side effects mentioned above, other symptoms have occasionally been reported during the use of stimulants, which disappeared abruptly when caffeine was discontinued, such as tremors, rapid heartbeat, circulatory problems, high blood pressure, nausea, mottled skin, or Raynaud’s syndrome.

About 50% of people with ADHD experience symptoms typical of an overdose (including severe overdose) when taking a single dose of stimulants in addition to caffeine they had previously tolerated without any problems. We know many people with ADHD who ignored this and therefore mistakenly believed they could not tolerate stimulants. A new attempt without caffeine and with a gradual increase in dosage, however, was often successful.

If you have been consuming large amounts of caffeine, you may experience caffeine withdrawal symptoms for 2 to 3 days after stopping. These symptoms often include headaches, exhaustion and loss of energy, restlessness, insomnia, circulatory problems, nausea, constipation, lethargy, irritability, and difficulty concentrating. These symptoms should not be mistaken for side effects of newly taken stimulants.

Once stimulants have been successfully tapered off, caffeine can be cautiously reintroduced. The difference is that people with ADHD then know that any side effects that occur are not caused by the stimulants.
We are also aware of reports from some people with ADHD who—after years of taking stimulants—still experience mild tremors even when drinking decaffeinated coffee.
Some people with ADHD report that they can use caffeine to prolong the stimulating effects that begin to wear off in the afternoon.

5.3. No concurrent nicotine withdrawal¶

Nicotine is a stimulant that increases dopamine and norepinephrine levels. Heavy smokers have therefore experienced a profound change in the balance of these neurotransmitters in the brain. Quitting smoking—especially overnight—leads to severe adjustment reactions and withdrawal symptoms. When we had him gradually reduce his intake, a former heavy smoker reported very severe and intolerable side effects, which disappeared when he started smoking again.
Even though smoking is harmful to your health, you should not quit at the same time as you start taking the medication.
In addition, when monitoring the drug’s effect during a single dose, it is helpful to avoid any external factors that might distort the results.
Unlike with caffeine, we have received reports of interactions involving nicotine much less frequently.

Often, people with ADHD lose their craving for nicotine during or after the titration period. In isolated cases, an increased craving for nicotine has also been reported.

5.4. Signs of an overdose¶

Symptoms of an overdose are usually the same as those of excessive caffeine consumption:⁶

• Tremors
• mild dysphoria
• Nervousness
• Heart palpitations
• Rapid heartbeat
• Headaches
• Irritability
• Circulatory problems

A loss of emotion (“zombie mode”) can be a sign of an overdose. For more information, see further down in this section.

It is difficult to distinguish between symptoms of an overdose and those of an underdose. If symptoms occur during titration at very low doses, one should always first attempt to increase the dose, while closely monitoring the subsequent symptoms. If the symptoms become milder or change entirely, they may be symptoms of underdosing.

5.5. Headaches¶

This description is based on Simchen’s *¹⁸³ * And is consistent with our experience.

5.5.1. Hypoglycemia¶

Headaches as a side effect of stimulant use are often consequences of low blood sugar.
Stimulants increase activity in the PFC, which boosts glucose consumption and lowers blood sugar levels.
Symptoms of hypoglycemia include

• Headaches
• Fatigue (yawning)
• Pallor
• Dizziness
• Tremors (though these may also result from an overdose or an interaction with caffeine).

Solution:

• Have a good breakfast / eat before taking each dose
• Snacks for in between meals
• If you get a headache, eat easily digestible carbohydrates right away
  • glucose
  • Bananas
  • Fruit juices (without sweeteners)

During prolonged hypoglycemia, the brain produces acidic metabolic byproducts through lactic acid metabolism, which lead to headaches that last longer and are more difficult to relieve.
People with ADHD often report that, as the effects of stimulants wear off, eating quickly can help them regain their concentration.

5.5.2. Dehydration¶

Another common cause of headaches when taking stimulants is insufficient fluid intake.

5.5.3. Histamine Intolerance¶

A third possible cause is histamine hypersensitivity or histamine intolerance, since all ADHD medications (with the possible exception of viloxazine) increase histamine levels. In such cases, however, the headaches occur alongside other typical symptoms of histamine intolerance.
Learn more about the symptoms of histamine intolerance at Histamine Intolerance, Histamine Sensitivity In the article Differential Diagnosis of ADHD

5.6. Gastrointestinal symptoms¶

Stimulants can increase gastrointestinal motility, which may be perceived as painful by people with ADHD (especially children).¹⁸³(

Higher doses taken on an empty stomach, in particular, can cause a strange, cramp-like sensation under the right rib cage about 30 minutes after ingestion. This is likely triggered by a spasm of the smooth muscle in the duodenum due to the sudden rise in stimulant levels.⁶

Solution:¹⁸³⁶
Eat a sufficient meal before taking the medication.
A longer interval before taking the medication (one hour) may be even more effective than a shorter interval (15 minutes).

5.7. Trouble falling asleep¶

Many people with ADHD report that since taking stimulants, they have been able to fall asleep more easily and enjoy more restful sleep.
However, some people with ADHD may experience difficulty falling asleep as a side effect of the initial dose. These symptoms usually subside within the first few weeks.

Solution:

• Take the last dose early enough so that its effects wear off at least one hour before bedtime
  • This requires knowledge of the typical duration of action of the respective medication. See Effects and Duration of Action of ADHD Medications
  • Increase the time interval if necessary
  • If necessary, skip the afternoon dose for the first 1 to 2 weeks and take only one dose of half-day-release MPH in the morning
• Consider the possibility of slowed metabolism (prolonged duration of action)
  • For more information, see Effects and Duration of ADHD Medications
• For some people with ADHD (we suspect this is more common in ADHD-I than in ADHD-HI), a reduced dose (1/5 to 1/2 of an optimized single dose) in an immediate release form may help them fall asleep
  • Try administering it as a sleep aid in very small doses (1/10 of the single daily dose)
  • Sustained-release daily doses must be converted to the equivalent dose of the immediate release form based on its shorter duration of action (for example, 20 mg of a sustained-release active ingredient with a duration of action of 5–6 hours is equivalent to 10 mg of the immediate release form with a duration of action of 2.5–3 hours).
• Avoid OROS-MPH (Concerta)
  • A comparison of two studies revealed a higher rate of difficulty falling asleep with OROS-MPH compared to Ritalin-LA.¹⁸⁴¹⁸⁵

5.8. Tachycardia (increased heart rate), elevated blood pressure, tremors¶

If these symptoms occur after taking stimulants, you should first make sure that you have completely avoided caffeine.

Stimulants stimulate the sympathetic nervous system.¹⁸³
MPH does not affect heart rate and increases blood pressure by 0.25. AMP and ATX slightly increase heart rate. Any cardiovascular effects subside spontaneously in most people with ADHD. 2% of people with ADHD discontinued their medication due to cardiovascular effects.¹⁸⁶ Once the body has adjusted, these effects do not recur even when the medication is resumed after prolonged treatment breaks.
Since the studies did not take caffeine interactions into account, some of the dropouts may have been due to caffeine.
According to the American Heart Association, carefully titrated stimulants for ADHD have no effect on the heart and do not require special monitoring in children and adolescents.¹⁸⁷

In particular, people with ADHD appear to experience a further rise in blood pressure when taking stimulants, even at carefully adjusted doses. If high blood pressure is under control before starting ADHD treatment, stimulants may be used, but blood pressure should be monitored at every follow-up visit.⁶

In people with ADHD, a more pronounced increase in heart rate may occur when the dose is adjusted. This should always be discussed with the doctor immediately.
Solution:

• slower dosing
• lower dosage
• Testing for cross-reactions
• Check whether caffeine has been completely omitted

5.9. Rebound¶

A rebound is a temporary increase in symptoms immediately after the effects of stimulants wear off. It is unpleasant but harmless and does not indicate any problems with the medication.⁶ Nevertheless, in some cases it can be so severe that people with ADHD consider discontinuing the medication.
Based on our observations, rebound occurs primarily with immediate release and half-day sustained release MPH. The rebound lasts about half an hour.
Full-day sustained-release formulations show less of a rebound effect.
Amphetamines have a lower risk of rebound than methylphenidate.⁶ In our experience, the extended-release formulation of Vyvanse has (almost) no rebound. In cases where a rebound effect has been reported with Vyvanse, our impression is that this primarily affects people with ADHD for whom a single dose of Vyvanse has a shorter duration of action (7 hours or less, instead of the 12 to 14 hours specified by the manufacturer).

Solution:

• Taking the next dose on time so that its effects begin just as the rebound is expected to occur
• A rebound effect after the last daily dose can be prevented by taking a small amount of immediate-release MPH
  • approximately 1/5 to 1/2 of the amount that would correspond to an optimal single daily dose (for medications with sustained release, this must be converted; see above under “Difficulty Falling Asleep”)
  • About 15 minutes before the expected rebound

5.10. Gaps in coverage¶

With sustained-release MPH formulations, some people with ADHD notice gaps in the effect between the first and second releases. This is a clear indication of rapid metabolism.
Sustained-release MPH formulations release multiple doses of MPH over time. If the first release is metabolized too quickly, its effect may already begin to wear off before the second release begins. In cases of such problems with fluctuations in active ingredient levels in MPH, it may be advisable to switch to full-day-acting MPH formulations within the MPH product range, such as Concerta, Kinecteen, or (the bioidentical alternative to Concerta) Neuraxpharm methylphenidate hydrochloride, which also provide 12-hour coverage, may be considered within the range of MPH formulations. Alternatively, switching to amphetamine-based medications should be considered, as these are metabolized differently, thereby increasing the likelihood of normal metabolism.

5.11. Loss of appetite / Weight loss¶

Stimulants and desipramine are often associated with the side effect of a decreased appetite and, consequently, weight loss. In most cases, this is merely a side effect associated with the initial dose and resolves over the course of a few weeks or months.

In cases of clinically significant weight loss, the following is recommended:¹²³

• Take medication not before, but during or after meals
• additional meals or snacks early in the morning or late in the evening (outside the times when the medication is effective)
• Nutrition Counseling
• high-calorie foods with high nutritional value
• planned break in treatment
• Change in medication

Since many people have trouble eating in the morning (for whom Medikinet Adult or Medikinet Retard is not suitable), care should be taken to eat a substantial meal in the evening.

It has been reported that loss of appetite may be less severe with Concerta than with other MPH medications.

Atomoxetine is also frequently associated with a loss of appetite, but the risk is slightly (by 12%) lower than with MPH (RR 0.82; meta-analysis, k = 8, n = 1,463)¹⁸⁸ Atomoxetine resulted in a weight loss of 0.6, Concerta in 0.9, and placebo in 1.1. (Thus, the placebo resulted in greater weight loss than ATX and MPH.)¹⁸⁹
The risk associated with methylphenidate and amphetamine-based medications was identical (RR 1.01; meta-analysis, k = 3, n = 414).¹⁸⁸
A survey conducted on the ADxS forum revealed (113 participants, as of April 2026):

• Lisdexamfetamine (LDX) was 44% more effective at suppressing appetite than methylphenidate (MPH)
• LDX and MPH were equally effective at suppressing appetite (30%)
• 26% MPH was more effective at suppressing appetite than LDX

Nortryptiline is said to be associated with weight gain as a side effect.¹⁹⁰

Adding low doses of antipsychotics could help prevent weight loss caused by stimulants.
While MPH was frequently associated with a loss of appetite, thioridazine was found to increase appetite as a side effect.¹⁹¹ Atypical antipsychotics are said to have an even stronger effect in terms of increasing appetite and causing metabolic syndrome.¹⁹²
Combination therapy with psychostimulants and antipsychotics is being used more and more frequently.¹⁹³ In isolated cases, improved efficacy compared to stimulant monotherapy has also been reported.¹⁹² A registry study found that 3.9% of children and adolescents with ADHD who were receiving stimulants were also being treated with atypical antipsychotics.¹⁹⁴ This opens up the option of using combination therapy to counteract excessive weight loss associated with stimulants.

Another option is to administer cyproheptadine.³¹
For more information, see Cyproheptadine for ADHD

If necessary, medication breaks may be required to help the patient regain weight.

5.12. Loss of Emotion / Zombie Mode: Overdose or Intolerance¶

In people with ADHD, particularly those with ADHD-HI and ADHD-C⁶, slowed thinking and blunted affect (emotional flatness) may occur (“zombie syndrome”). In such cases, avoiding an overdose or reducing the stimulant dose as part of a combination therapy with non-stimulants can help. For more information, see Combination Therapy for ADHD

There is absolutely no need to accept a reduction in emotionality as a side effect of ADHD medication. ADHD medication works properly when the person with ADHD feels more like themselves. Any sense of feeling like a stranger to oneself—or of feeling less like oneself—is a sign that the medication is not the right fit.
Stimulants suppress the limbic system. A small number of people with ADHD are particularly sensitive in this regard. In most cases, persistent trying out different medications and active ingredients helps.
In our experience, emotional blunting is more often a consequence of an overdose. In such cases, restarting the dosage regimen with the smallest possible increments should be considered. Some (albeit very few) people with ADHD require only a few milligrams of a stimulant throughout the entire day.

The following options should only be considered once it has been determined that a dose reduction—at which the emotional impairment is just barely avoided—does not sufficiently improve ADHD symptoms:

• Atomoxetine or Guanfacine Instead of Stimulants
  • Non-stimulants
    • Do not inhibit the limbic system
    • Do not improve the drive
• Reducing the dose of stimulants when co-administered with non-stimulants (Advantage: The motivation provided by stimulants is maintained, and emotional dysregulation is improved throughout the day)
  • Adults: Stimulants and Atomoxetine
  • Children: Stimulants and guanfacine or stimulants and atomoxetine

5.13. Cycle-Related Fluctuations in Symptoms in Women¶

Dopamine levels are influenced, among other factors, by COMT. COMT is the primary degradation mechanism in the PFC, whereas degradation in the striatum is primarily regulated by DAT.
Metabolism is strongly influenced by the COMT gene variant.
A significant proportion of women with ADHD report more severe symptoms during the premenstrual phase. If the patient is taking stimulants, this can be alleviated by temporarily increasing the stimulant dose during this phase. One study reports positive results from increasing the stimulant dose by an average of 41% during the premenstrual week.¹⁹⁵

5.14. Variable Effect¶

Sometimes, even after a prolonged period of stable effects, people with ADHD report fluctuations in the drug’s effects.
There are many possible causes. For more information, see Effects and Duration of ADHD Medications
Examples:

• other medications that have been added or discontinued
  • In particular, for ADHD medications:
    • Anticides
• Interactions with food
  • There are many options here. Keep a food diary
  • in particular
    • Grapefruit
    • Vitamin C
      • If necessary, delay taking the medication by one or more hours after taking the other medication
• Changes in stomach acid
  • MPH and AMP are sensitive to changes in stomach acid
  • Measure the urine’s acidity, if necessary
• Defective drug batches
  • rare, but we’ve actually experienced it several times
  • Did the effect change when you started a new package?
• Medications stored in too hot a place
• Adaptive responses
  • rarely, after prolonged use with consistent results
  • For more information, see Medications: Development of Tolerance

5.15. Symptoms of Overwork¶

After starting medication, many people with ADHD become highly active as they tackle their problems and tasks.
For some people with ADHD, this can lead to symptoms of stress and, in some cases, even a breakdown.

We do not consider this to be a pharmacological consequence of the medication, but rather a psychological one. In particular, it is not a manifestation of hyperactivity or inner restlessness; on the contrary, it represents a significant increase in effectiveness and work intensity compared to the period before the medication was started.

Thanks to the medication, many people with ADHD are now better able to motivate themselves and therefore think they can now accomplish everything they want, should, or feel they have to do.
But there’s a difference between being able to do “more” and being able to do “everything.”

While medication does allow you to get more done now, it doesn’t restore your full capacity. Although it often enables people to reach the same level of performance as those without the condition, this isn’t always the case, nor does it apply to everyone. Medication also doesn’t give you superpowers that would suddenly let you accomplish everything you’ve always wanted to do.
Subjectively, however, this isn’t noticeable. From the inside, you just feel that you’re doing better now. You can’t sense that this still isn’t the whole story, because you’ve never known anything else and don’t know what it would be like to no longer have ADHD. This is also where a conflict with an internal, dysfunctional perfectionism might come to light.

Therefore, especially shortly after taking the medication, people with ADHD should take particular care not to overexert themselves.
When taking medication, you first have to get to know your new limits—what’s possible now and what you can reasonably expect of yourself.
Medications can shift these boundaries, but they cannot eliminate them.

5.16. Raynaud’s (Circulatory Disorder Affecting the Fingers)¶

ADHD medications can trigger or worsen Raynaud’s. Raynaud’s has been observed less frequently with atomoxetine than with stimulants. ¹⁹⁶ It has been reported that reducing the dose, tapering off the medication, or switching to a different active ingredient was less likely to help. However, there have also been (very rare) reports of serious Consequences.
We are aware of cases in which Raynaud’s syndrome was triggered by caffeine consumption while taking ADHD medication and resolved after caffeine was eliminated from the diet.

6. General Information¶

• For dose titration, immediate release MPH should be used during the first week or so. The shorter duration of action and the more linear dose-response relationship (without a second peak when the portion with sustained release begins to take effect) make it easier to determine the appropriate dose, especially for inexperienced observers (both people with ADHD and third parties).
• With sustained-release Medikinet, it is important to note that it must be taken with food; otherwise, the entire dose will be released in immediate release form. Other medications generally do not require food, although this should always be verified in the package insert. For all long-acting ADHD medications, it is recommended to take them with food.
• Caffeine (coffee, cola, black tea, some green teas, mate, energy drinks) and dark chocolate/cocoa (theobromine) must be completely avoided during the titration phase. Many people with ADHD can no longer tolerate caffeine or other stimulants while taking stimulant medications, even though they previously consumed them without any problems or even in larger quantities. Caffeine (theine) and theobromine are stimulants that also increase levels of norepinephrine and dopamine. They can have an additive effect when combined with ADHD medications. This can easily be mistaken for an overdose (internal restlessness, agitation, trembling).
  After the dose has been administered, caffeine can be consumed again, though it is recommended to test it cautiously at first. If caffeine now causes tremors, it is clear that this is due to the caffeine and not the medication.
• Alcohol increases blood levels of MPH and must be completely avoided when taking a single dose of MPH.
• Avoid citrus fruits while adjusting your medication dosage. Some people with ADHD experience varying effects on their medication when consuming citrus fruits. Grapefruit should be avoided whenever adjusting your medication dosage.
• Attendance on afternoons, weekends, and during school breaks
  • Since ADHD is not purely a school-related issue—even though it manifests particularly clearly in that setting due to extrinsic demands and learning difficulties caused by a lack of neurotrophic factors—continuous medication is strongly recommended. Whether medication should be taken only in the mornings during school hours depends on whether the people with ADHD are still able, with this medication, to concentrate on their homework and manage their social interactions without emotional dysregulation and without symptoms until early evening.
  • You should avoid stopping medication on weekends or during school breaks. For one thing, symptoms don’t strictly follow the school schedule, and for another, a longer break in treatment may require gradually reintroducing the medication to avoid side effects.
  • However, it is possible to reduce the dosage slightly during periods of lower demand (to 2/3 or 3/4). This depends very much on the individual needs of the people with ADHD. Any changes to the dosage must be discussed with the doctor. An experienced doctor, however, will grant a trusted patient considerable leeway.
• Mixing Stimulants
  • Stimulants can be combined. In particular, sustained-release and immediate-release medications can be taken on the same day. A combination of AMP and MPH also does not cause any particular problems.
    As a general rule, a sustained release form of the medication is taken during the day, which ideally provides coverage for the entire day. Responsible and trustworthy patients can supplement their treatment with immediate release MPH to manage occasional special situations, such as a particularly long evening.
    The instructions of the attending physician are binding!
• The menstrual cycle can significantly affect how medications work.
  • When considering fluctuations in the effects of medication in women, one should take into account the significant influence that estrogen may have on certain COMT gene variants. A dosing guide that helps track menstruation and its effects can be found at ADHD-Forum.ADxS.org.