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Medication dosage for ADHD

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Medication dosage for ADHD

Like all presentations on medications at ADxS.org, this information is compiled solely from a scientific perspective. It is not intended for self-medication, but to enable well-informed discussion with the treating physician and to understand his instructions.
Each specific treatment must be based on the instructions of the attending physician for the individual case.

Setting the optimal dosage of medication for ADHD depends on the type of medication.

1. Medication adjustment of stimulants

Stimulants such as methylphenidate or amphetamine drugs have an immediate and dose-dependent effect.

1.1. Dosage not flat rate or according to body weight

There is still a widespread misconception that stimulants should be dosed in relation to body weight. There may be a statistical mean of which dosage might be more often appropriate at which body weight. However, since the neurotransmitter imbalance to be corrected does not correlate with weight, each dosage is an individual matter. A blanket assumption of a statistical mean would be a treatment error. An upper dosage limit of 1 mg / kg MPH is usually a good guide to avoid increased side effects. However, in individual cases (with correspondingly rapid metabolism), significantly higher dosages have been required and tolerated. Adults often require lower dosages than adolescents or children. In individual cases, the optimal dose may be below 5 mg / day.

1.2. Order of the means of choice

1.2.1. Means of choice for children

  • First choice is methylphenidate
  • Second choice is amphetamine drugs
  • Third choice, in our opinion, is guanfacine (especially for hypertensive reactions to MPH and AMP or for comorbid tics), which statistically has a much better effect size with fewer side effects than atomoxetine
  • Fourth choice is atomoxetine. It may be first choice for SCT or severe ADHD-I.
  • For other possible medications, see related articles

1.2.2. Means of choice for adolescents

  • First choice continues to be methylphenidate
  • Second choice is amphetamine drugs
  • Third choice, in our opinion, is guanfacine (especially for hypertensive reactions to MPH and AMP or comorbid tics), which statistically has a much better effect size with fewer side effects than atomoxetine.
  • Fourth choice is atomoxetine. It may be first choice for SCT or severe ADHD-I.
  • For other possible medications, see related articles

1.2.3. Means of choice for adults

  • First choice is amphetamine drugs
  • Second choice is methylphenidate
  • Third choice is atomoxetine. It may be first choice for SCT or severe ADHD-I.
  • Fourth choice, in our opinion, is guanfacine, as the positive efficacy reports of guanfacine are primarily for children
  • For other possible medications, see related articles

1.3. Guide to the dosage of stimulants

Stimulants include methylphenidate and amphetamine medications.

In our opinion, the procedure described below is recommended.
The method of use prescribed by the respective physician is quite explicitly decisive.

1.3.1. Dosage

Dosing can be done with unretarded MPH or retarded agents.
Unretarded MPH allows better control of symptom improvement on the one hand, but on the other hand requires more reliable patient compliance due to the higher number of single doses / day. Therefore, in children and especially in younger children, single dosing with sustained-release medication may be recommended.

1.3.1.1. Dosing with unretarded MPH
  • Start with a one-time very low dosage (2.5 mg unretarded MPH ) and deliberately expect no effect at all.
    Purpose:
    Carefully accustoming the body to the drug to avoid side effects that would otherwise have to be overcome, which could lead to avoidable discontinuation.123
  • Then 2.5 mg unretarded twice a day.
  • Further increase in the number of single doses until the day is covered.
    Since unretarded MPH is effective for only 2.5 to 3 hours, 3 to 5 single doses are required for daily coverage. With two doses, almost the entire day would remain unmedicated. This could completely distort the assessment by affected individuals or third parties, especially if they have not been educated about the limited effective time window (and the expected rebound). Most importantly, it would not sufficiently reduce the symptomatology and thus the burden on the affected person.
  • Thereafter, every 4 to 7 days, increase the dosage by a maximum of 2.5 mg / single dose.
    We consider dose jumps of 5 mg unretarded MPH / single dose to be disadvantageous.
  • Purpose: Slow up-dosing avoids skipping the optimal dose.
    Not all, but a significant proportion of those affected have, in our experience, a very narrow window for an optimal dosage of well below 5 mg, so that 2.5 mg less / single dose is not sufficient and 2.5 mg more can already trigger the first overdose phenomena. It is likely that so far quite often an intolerance was assumed, which in reality was due to inappropriate dosages.
    Since such small-dose increments do not harm other sufferers (but, on the contrary, help avoid single-dose side effects),4 dosing increments in 2.5-mg increments (relative to an unretarded single MPH dose) should be the gold standard. So, too, does Kühle.5
    Other sources recommend a start with 1-2 single doses of 5 mg and a weekly increase of the single dose in 5 mg steps.6 For the reasons mentioned above, we consider these dose jumps to be too large and expressly advise against them.
  • Inform affected persons and (initiated) observing third parties about the duration of action of the respective preparation and the expected rebound.
    Knowing the duration of action, in addition to expecting when an effect will occur and end, is further important for taking the last dose in time before going to bed so that the effect has worn off at least an hour before. In some sufferers (we suspect more in ADHD-I than ADHD-HI), a reduced dose (1/5 to 1/2 of an optimized single dose) in unretarded form may help with falling asleep. Again, test administration as a sleep aid with very low doses (1/10 of the single daily dose). Retarded daily doses are to be converted to the unretarded effective time. (Example: 20 mg sustained release for 5-6 hours action time corresponds to 10 mg unretarded for 2.5-3 hours action time).
  • Increase the dosage until a very satisfactory effect is achieved.
  • At a daily dose of 20, 40, 60 mg MPH, a feedback discussion should be held with the treating physician in each case.
  • In addition, it is recommended to keep a diary (see below). Some physicians expect a weekly transmission of the diary, e.g. by mail. This can help to detect undesirable developments at an early stage.
  • After reaching the supposed optimal dose, make 2 more increases to find that negative symptomatology is now added.
    Purpose:
    It is ensured that not only an improvement of the symptomatology but also the optimal dose is determined. Furthermore, the affected person learns how it feels when there is a slightly too high dosage. This is important so that the affected person develops a feeling for what the optimal dosage is, in order to be able to stimulate further dosage reductions if necessary.
  • It is possible that side effects may occur at certain dosage levels that disappear at higher dosage levels. In particular, internal tremors (like one too many cups of coffee) may disappear within 2 to 3 days after a dose increase. It is possible that this is an adaptation of the noradrenergic system. Several sufferers have reported to us that at the next dose level, or the one after that, this internal tremor disappeared again. If it becomes more pronounced or persists permanently, it is a sign of overdose
  • “Zombie” symptomatology indicates either overdose or unmasked depression
    • Stimulants close stimulus filters: This is probably the reason why students “try out” stimulants for stressful exam times (which we strongly advise against), but do not continue taking them afterwards of their own accord.
    • Those who (unlike ADHD sufferers) do not have a stimulus filter that is too wide open lose quality of life as a result. There are no reports of students taking MPH voluntarily outside of very stressful exam periods.
    • Stimulants inhibit the limbic system. An overdose can therefore lower the emotional sensation.7
  • In rapid metabolizers (about 15-20% of those affected), unretarded MPH is effective for only about 1 to 1.25 hours instead of the usual 2.5-3 hours, Medikinet or Ritalin adult for only about 3 hours instead of the usual 5-6 hours, and Elvanse for 5-7 hours instead of the usual 10-12 hours. The rapid metabolizers we knew reported that they tolerated appropriately more frequent doses and appropriately higher daily doses well without any side effects. Nevertheless, with the increase in the number of doses/day required here and the consequent possible exceeding of the general maximum dose recommendations, closer monitoring is certainly required.
1.3.1.2. Transition to sustained release MPH / AMP
  • Once discontinuation with unretarded MPH has occurred, the number of single doses/day should be reduced by using sustained-release preparations.
1.3.1.3. AMP dosing
  • Since in adults Elvanse is the drug of choice (highest effect size and lowest side effects among all ADHD drugs), direct dosing with Elvanse is often attempted.
  • Elvanse adult is available in capsules of 30, 50, and 70 mg; Elvanse (without “adult”), which is completely identical except for dose sizes, is available in sizes of 20, 30, 40, 50, 60, and 70 mg.
  • 30 mg for single dose involve a significant risk of overdose and increase the risk of dosing side effects
    Optimal dosage levels are 5 mg. We know several patients for whom the optimal dosage range of Elvanse is below a margin of 5 mg. 5 mg less is too little, 5 mg more is overdosed. We also know individual sufferers who are optimally dosed with 3 mg Elvanse / day.
  • Although the package insert does not allow the contents of the capsules to be divided up, many years of experience have shown that this is the most sensible way for dosing and for finding the optimum dose for a large number of patients. We do not know of any reports of fluctuations in effect due to uneven distribution of the active ingredient. Fine dosage can be achieved by dissolving the contents of the capsule in water and dividing it by means of a syringe with almost milligram precision. So too does Kühle in the equivalency table.8. A somewhat coarser method is to divide capsules into equal-sized heaps using a razor blade on a glass surface.
  • The dissolved Elvanse keeps in the refrigerator for a few days.
1.3.1.4. Duration of action of single doses and daily coverage
  • Affected persons should be explicitly informed about the duration of action of a single dose of the respective preparation during dosing. We repeatedly receive reports from patients who were led to believe that a single dose of unretarded or half-day-retarded MPH (e.g., Medikinet) would be effective throughout the day, instead of being advised of the usual duration of action of 2.5 - 3 or 5-6 hours. This naturally leads to erroneous feedback to the physician when it is reported that the symptomatology is unchanged because, in ignorance of the duration of action, it was set to the afternoon or evening.
  • Unretarded MPH acts for about 2.5 - 3 hours, the “normal” half-day retarded MPH preparations (Medikinet,m Ritalin adult) for about 5- 6 hours, some MPH full-day retard preparations (Concerta, Kinecteen) as well as Elvanse idR for about 10 - 12 hours. Daytime coverage requires medication for about 14 to 15 hours, which is hardly achievable with a single dose.
  • C. 15 - 20 % of those affected are fast metabolizers. For this, see above.

1.3.2. Diary documentation and external observation

During the dosing period, a diary should be kept to record how the patient is feeling each day. This should contain:

  • Present symptoms (identify using overall symptom list: *⇒ Total list of symptoms of ADHD according to manifestations
  • Note change for each symptom
    optimal, but hardly feasible, would be a quotation with 24 hours to 48 intervals to avoid overvaluation of individual moments
  • Dose
  • Intake date(s)
  • Other medications taken (type, dose, time(s))
  • Food intake (type, quantity)
  • Menstrual cycle in girls / women
    More on this at Gender differences in ADHD
  • Sports
  • Special stresses (emotional as well as physical, e.g. quarrels, illnesses, allergies, etc.)
  • Important: the evaluation of the effect of the drug and the dosage is not done on the basis of individual days, but always in retrospect on the basis of an average of 3-4 days. Otherwise, irrelevant and random correlations are overestimated.

It is also helpful to discreetly ask uninitiated third parties about any changes they have noticed. It must be expressly warned against informing these third parties that medication is being taken, as this would always have the effect that their attitude to medication would be subconsciously included in the assessment and change the result.
With children, it can be very helpful not to tell them themselves that they are now receiving medication, but to refer to it as vitamins during the dosing phase. After a few weeks, discussions with the teachers, who are also not in the loop, can be informative as to whether they have noticed any changes.

1.3.3. Side effects

  • Mild side effects (dry mouth, headache or similar) usually pass within a few weeks
  • More severe side effects (aggressiveness, hypertension or other) immediately discuss with doctor.
  • Rebound
    Rebound is a brief increase in symptoms immediately after the end of the active period of stimulants. It is unpleasant but harmless and does not indicate problems with the drug. It occurs, in our impression, primarily with unretarded and semiretarded MPH. The rebound lasts about half an hour. It can be avoided by taking the subsequent dose in time.
    All-day retard preparations show less rebound.
    Elvanse has no rebound.

1.3.4. Change of preparation and active ingredient

If a medication does not show any effect (nonresponding), the first step should be to switch to another MPH preparation, especially in the case of MPH. Surprisingly often, patients react negatively to one MPH preparation and positively to another MPH preparation, while it can happen the other way around.

If an active ingredient shows no effect overall (regardless of the preparation) (nonresponding), another active ingredient should be tried first.
30% of all patients do not respond to MPH, and 30% do not respond to AMP (nonresponders). However, this nonresponding is staggered and rarely affects both agents at the same time, so that 90% of those affected react to either MPH or AMP.

1.3.5. Dosage adjustments

  • The sensation that a very good effect after the first cessation wears off after a few days to weeks is often not due to a change in effect but to a change in the way the affected person feels. In the so-called honeymoon phase immediately after reaching an effective dose, the difference from the deficient state before is perceived as a particularly positive experience. Such a feeling of a special improvement is naturally transient, just as the elation of a soccer fan after winning the championship returns to normal within days, although the whole season was trembling along. In this case, it must be carefully examined whether there is really a need for a higher dosage. External assessments can be helpful here.
  • It may happen that a readjustment is required once after a few months. This does not represent a habituation effect.
  • An omission test should be done once a year to check if the behavior continues to show AD(HHD) symptoms without medication.
  • ADHD sufferers frequently show 75% of the possible ADHD symptoms, non-affected people 12 to 25%. The goal of optimal dosing is therefore not complete freedom from symptoms, but a reduction of symptoms to a healthy level. An attempt to increase the dosage until all symptoms are completely eliminated would inevitably end in an overdose.

1.3.6. General notes

  • For dosing, unretarded MPH should be used for approximately the first week. The shorter duration of action and the more linear dose-response correlation (without a second high at the onset of action of the retarded portion) facilitate finding the appropriate dose, especially for inexperienced observers (affected persons as well as third parties).
  • In the case of retarded medicinet, it must be noted that this must be taken together with food, otherwise the entire dose will be delivered unretarded. Other medications should be evaluated for the need to take food at the same time. For all long-acting AD(HS drugs, it is recommended to take them together with food intake.
  • Omit caffeine (coffee, cola, black tea, some green teas), dark chocolate / cocoa (theobromine) as well as alcohol during dosing, and try very carefully later. Many affected persons can no longer tolerate caffeine or other stimulants when taking stimulants, which were previously consumed without problems or even in larger quantities.
    Caffeine (teein) and theobromine are stimulants. They can add up with ADHD medications. This can quickly be mistaken for an overdose (internal jitteriness, inner restlessness, tremors). Alcohol increases the MPH blood level.
  • Avoid citrus fruits during dosing. Some affected individuals react to citrus fruits with varying drug effects. Grapefruit should be avoided during any medication dosing.
  • Informing distant third parties or caregivers during dosing
    • In order to avoid a bias in the assessment of the effect by teachers or other caregivers, it can be advantageous not to inform them about the intake at first. If they then report a significant change in behavior within the first few weeks, this unbiased observation is more reliable.
    • If the observers know the medication, the report will always also reflect the observer’s opinion about the (supposed) effect of this medication. Obtain reports inconspicuously.
    • Reports only make sense if the duration of action of the medication is long enough. An unretarded tablet in the morning cannot produce any changes beyond the 2.5 to 3 hours of action.
  • Taking in the afternoons, weekends and vacations
    • Since ADHD is not a purely school-related problem, even if it is particularly evident there due to the extrinsic demands and the learning problems caused by the lack of neurotrophic substances, continuous medication is urgently recommended. Whether medication should only be given in the mornings during school hours depends on whether those affected are still able to manage their homework in a concentrated manner and their social contacts without emotional dysregulation until the early evening without symptoms.
    • Stopping the medication at weekends or during vacations should be avoided. On the one hand, symptoms do not adhere to school hours in a very disciplined manner and, on the other hand, a longer break in taking the medication may require that it be dosed again slowly in order to avoid side effects.
    • However, it is conceivable to reduce the dosage somewhat (to 2/3 or 3/4) in times of lower demands. Here it depends very much on the individual needs of the person concerned. All dosage changes must be coordinated with the physician. However, an experienced physician will allow a trustworthy patient considerable room for maneuver.
  • Mixing stimulants
    • Stimulants can be mixed. In particular, sustained-release and non-released drugs can be mixed. A mixture of AMP and MPH is also problem-free.
      As a rule, a sustained-release form of medication will be taken during the day, optimally covering the entire day. Responsible and trustworthy patients can cover isolated special stresses, e.g. a particularly long evening, by means of unretarded MPH as a supplement.
      The instructions of the attending physician are authoritative!
  • Menstrual cycle can strongly influence drug effect
    • For variations in drug effects in women, the significant influence of estrogen, which is possible with certain COMT gene variants, should be noted. A dosing guide table to assist in mapping menstruation and its effects can be found at ADHD-Forum.ADxS.org.

1.4. Stimulant discontinuation

From a medical point of view, stimulants can be discontinued quite easily from one day to the next. Apart from the recurrence of symptoms and the reappearance of side effects when dosing again after a longer break from medication, we are not aware of any typical disadvantages, especially withdrawal symptoms.
Nevertheless, always consult the attending physician.

2. Dosing of level medication

By level drugs, we mean medications that must first be taken over a longer period of time before they show an effect. Classic representatives are serotonin reuptake inhibitors (e.g., SSRIs, selective serotonin reuptake inhibitors). These develop their effect only after 14 days to 4 weeks. They do not act directly by changing serotonin levels, because this occurs very quickly, but presumably by down- or upregulation of receptor systems, which then mediate the actual effects.

2.1. Serotonin reuptake inhibitor

The use of serotonin reuptake inhibitors must always be coordinated individually with the physician. Serotonin reuptake inhibitors are suitable for the treatment of (comorbid) depression.
With regard to ADHD, treatment of impulsivity in ADHD-HI by minimal doses (e.g., 2 to 5 mg escitalopram) might be useful at best, which in our experience seems to act immediately and does not appear to be mediated by receptor downregulation or upregulation.
Incidentally, serotonergic medications are not useful with respect to ADHD itself and especially ADHD-I.

2.2. Norepinephrine reuptake inhibitor

Noradrenaline reuptake inhibitors can have a positive effect in ADHD. It should be noted, however, that noradrenergic drugs in ADHD often show a positive effect only in the first few days, which then subsides within one or two weeks. This could be due to the fact that in ADHD the phasic noradrenaline level is impaired, but not the tonic one. However, it is also conceivable that the frequently observed fading of the effect of noradrenergic drugs is due to a down- or upregulation of receptors. However, this is contradicted by the fact that such a down- or upregulation usually requires 14 days or longer and is not noticeable after only a few days.
Purely theoretically, it is conceivable that medication in a multi-day rhythm could show the benefits more long-term (taking everything 2, 3 or 4 days instead of daily).
Unlike norepinephrine reuptake inhibitors, guanfacine, as a selective postsynaptic α-2A-adrenoreceptor agonist, appears to increase phasic rather than tonic norepinephrine.

2.3. Tapering level medication very slowly

Level medications must be dosed slowly and phased out slowly.
For serotonin reuptake inhibitors, this can take up to more than half a year to avoid side effects.

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