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Medication for ADHD - Overview


Medication for ADHD - Overview

All described medications should always be prescribed by experienced physicians/neurologists only. Our explanations are only intended as impulses for a personal discussion with a doctor.

Since ADHD symptoms originate quite predominantly from the dopaminergic and noradrenergic systems, combined medication with dopaminergic and noradrenergic agents is recommended.12345

Medications for ADHD unfortunately do not work in a curative way. They only act as a correction of the neuronal dysfunctions - like glasses that correct an existing defective vision as long as they are worn.

1. Drugs affecting stress response

By influencing the stress response, we do not mean sedative or other general effects, but effects of drugs on the response of stress regulatory systems.

1.1. Anxiolytics

Anxiolytics (anxiety-reducing drugs), even in single doses, generally reduce the reactivity of the stress systems.6

1.2. Antidepressants

Single doses of antidepressants have partly inhibitory and partly activating effects on stress systems.6

1.3. Stimulants

1.3.1. Stimulants and stress resistance

Stimulants stimulate the reactivity of stress systems.6
Stimulants are able to bring the attentional control of ADHD sufferers into line with that of non-affected persons by raising motivability.7 This might (partly) explain why stimulants are as helpful in ADHD-HI and ADHD-C as in ADHD-I. For more on the deviant function of the DMN in ADHD and its normalization by stimulants, together with further references, see DMN (Default Mode Network) In the article Neurophysiological correlates of hyperactivity.

1.3.2. Stimulants and emotions

Barkley8 explained in a lecture that stimulants can dampen emotions by inhibiting the limbic system. The higher the dosage, the more the limbic system (including the amygdala) would be inhibited. This, by its very nature, reduces affect.
Too high a dosage of stimulants therefore leads to restricted emotions, he said.
He goes on to report that for this reason, mixed drug regimens are increasingly being used to preserve the major advantage of stimulants and limit the disadvantages.

1.3.3. Long-term compliance - phases of taking medication

It is often observed that stimulants are discontinued by ADHD sufferers some years (about 1.5 to 3 years) after the initial prescription. A few years later (about 4 to 6 years after the initial prescription), increased intake occurs again.9

Our hypothesis is that this return to increased intake may also be mediated by the following mechanism, among others:

Stimulants have been shown to increase neuroplasticity by increasing dopamine and other neurotrophic factors. This enables better learning (i.e., knowledge acquisition) and better adaptation of experiences in the sense of internalization/automation of functional behaviors as an adaptation process to environmental experiences. For more, see Neurophysiological correlates of learning problems in ADHD.
Taking stimulants now allows functional behaviors to adapt to current demands.
If this adaptation has occurred sufficiently after a few years, a short-term discontinuation of stimulants does not lead to immediately deficit behaviors, because the currently stored behavior patterns are now adapted to the current environment and therefore continue to function for the moment even without medication.
However, with continued non-administration of the medication, the constantly necessary adaptation of the behavioral patterns to new environmental requirements fails to take place. As environmental demands gradually change, the stored behaviors that were optimized to meet earlier environmental demands become increasingly dysfunctional. When the difficulties have reached a certain level again, the suffering pressure reminds the patient that the medication helped very well against these difficulties at the beginning, which leads to a renewed intake of medication.

The self-reported reasons for discontinuing medication in parents are often a distrust of medication (concern about side effects, weight loss, growth retardation) while adolescent sufferers themselves give completely different motives, namely the desire to develop freely without medication.10

2. Dopaminergic drugs

Dopaminergic drugs have the leading role in ADHD, as most symptoms are caused by dopamine (effect) deficiency in the dlPFC and striatum.

Dopaminergic medications have the further benefit, concomitant to psychotherapeutic interventions, of increasing brain neuroplasticity and thus supporting therapy efficacy or establishing therapy capacity.11
About 5% of dopamine is metabolized into norepinephrine, so dopaminergic drugs always have a simultaneous (albeit small) noradrenergic influence.1112

Dopaminergic drugs address the anterior center of attention.
The dopaminergic and noradrenergic attentional centers.

3. Noradrenergic drugs

Norepinephrine is formed in the nucleus coeruleus and controls, among other things, the posterior center of attention in the parietal cortex.
The dopaminergic and noradrenergic attentional centers.

3.1. Drugs that increase norepinephrine levels

Norepinephrine reuptake inhibitors increase the amount of available norepinephrine. Pure norepinephrine reuptake inhibitors are the “second choice” along with dopaminergic and noradrenergic stimulants. However, they can support medication with MPH when appropriate.

MPH, amphetamine drugs, and atomoxetine each act dopaminergically and noradrenergically, with atomoxetine acting noradrenergically and dopaminergically only in the PFC , whereas MPH additionally acts dopaminergically in the striatum.
Effect of atomoxetine different from MPH

3.2. Effect of noradrenergic drugs

The effect of noradrenergic medication is subjectively described by ADHD sufferers as increasing the “green zone” between underchallenge (which makes ADHD sufferers shut down internally), and overchallenge (which drives ADHD sufferers into stress). Balance increases. Affect breakthroughs (outbursts of anger, emotional overreactions) decrease.

Noradrenergic medication improves ADHD symptoms

  • Affect breakthroughs (outbursts of anger)
  • Emotional impulse control
  • Wakefulness
  • Vigilance

Dopaminergic drugs cannot directly affect these symptoms (at best, through the norepinephrine that results from the breakdown of dopamine).
Likewise, amphetamine medications are said to be helpful here.13

Augmenting optimal adjustment with noradrenergic medications can subjectively double the gain that methylphenidate produces. (Individual) sufferers report that an optimal setting dosage in combination with stimulants completely eliminated ADHD symptoms in them. Unfortunately, this effect was temporary, suggesting up- or downregulation of receptors (see 2.4.).

3.3. Response rate of noradrenergic drugs

Primary noradrenergic medications usually need to be flooded for 2 to 3 weeks before they take effect.
Discontinuation of noradrenergic drugs should be gradual over the same period of time to avoid depression.
Because of the slow dosing response, noradrenergic medications should not be increased, omitted, or discontinued in the short term.
The speed of response is similar to that of serotonin reuptake inhibitor drugs.

3.4. Long-term effects of noradrenergic drugs problematic

The effect of noradrenergic drugs may diminish somewhat after some time (unlike that of stimulants).

We suspect that most noradrenergic medications act tonically, i.e., cause a long-term increase in NE levels. However, ADHD symptoms improve only with a phasically increased noradrenaline level. A tonically increased NE level is even counterproductive.14
Many ADHD sufferers have noted a short-term positive effect of noradrenergic medication (e.g., nortryptiline), which was already effective with the first tablets but disappeared again after a few days. Individuals with atomoxetine also reported this as an individual reaction.

This is followed by Scheidtmann’s remark that noradrenergic drugs (e.g., antidepressants) do not help in motor rehabilitation (if) they are used as permanent medication, because tricyclic antidepressants stimulate noradrenergic receptors permanently and this leads to a loss of receptor sensitivity (especially with respect to learning processes) as a result.15
This is consistent with experience with the use of noradrenergic tricyclic antidepressants in ADHD. Here, it is often reported that initially there is a very good response, which, however, decreases with continued medication.

While dopaminergic medications can be discontinued for hours or days at a time or increased for short periods without any problems, noradrenergic medications should be cautioned against this. Noradrenergic drugs carry the risk of depression in the event of overdose and sudden fluctuations in dosage.

A clearly structured daily routine, in which activity and breaks are sensibly alternated, should train the noradrenergic system and help to normalize the production of noradrenaline again.16

3.5. Contraindications

Benzodiazepines reduce the activity of the locus coeruleus And thus reduce the production and transport of norepinephrine to other parts of the brain. Therefore, they would have to be contraindicated in ADHD in general. Surprisingly, however, they are helpful in the short term: but because of their massive dependence potential, which occurs after only 14 days at usual doses, they should not be prescribed. MPH and amphetamine drugs, on the other hand, have no dependence potential.

In addition, there are other side effects and interactions.

4. Serotonergic drugs

4.1. General information about SSRI

4.1.1. Response speed of serotonergic drugs

Although serotonin levels are altered by serotonergic medications in the very short term, serotonergic medications usually need to be flooded for 2 to 3 weeks before they take effect. Therefore, it can be assumed that the serotonin level itself does not mediate the actual effect.

The increase of serotonin in the synapse by serotonin reuptake inhibitors activates feedback mechanisms: serotonin-1A and serotonin-B autoreceptors both inhibit serotonin transmission. If this inhibition is maintained for a longer time, the inhibitory serotonin autoreceptors become desensitized, which reduces their inhibitory influence. As a result, serotonergic neurotransmission increases. Since desensitization of serotonin-1 autoreceptors takes time, the onset of action is delayed to this extent.17

Adaptive down- or upregulation of receptor systems or neuroplastic processes are assumed as further mechanisms of action.18

Discontinuation of serotonergic medications should be phased out over at least the same period of time to avoid depression. According to other reports, the discontinuation of serotonergic drugs can last up to more than half a year to avoid side effects.

Because of the slow dosing response, serotonergic medications should not be increased, omitted, or discontinued for short periods of time.

4.1.2. SSRIs and σ-receptors SSRIs according to binding strength at the σ1-receptor

Sort descending

  • Fluvoxamine19
    • Less affine, but highly selective at the serotonin transporter
    • Sigma-1 agonist
      • Remedies depression-typical cognitive losses19
      • Improves psychotic symptoms19
      • Enhances nerve growth factor-induced neurite growth in PC12 cells19
  • Sertraline19
    • Sigma-1 antagonist
      • Remedies depression-typical cognitive losses19
      • Worsens psychotic symptoms19
      • Decreases nerve growth factor-induced neurite growth in PC12 cells19
  • Fluoxetine19
  • Citalopram19
    • Escitalopram is the active S-enantiomer of racemic citalopram.20
  • Paroxetine (almost no binding)19
    • Paroxetine also has an anticholinergic effect
      can thereby trigger concentration difficulties and forgetfulness19

4.1.3. SSRI single doses increase anxiety and risk of panic attacks

Single doses of escitalopram increased the risk of panic attacks.21 Anxiety and tension was likewise increased by a single dose of chlorimipramine/chloromipramine/clomipramine, a tricyclic antidepressant that acts primarily as a serotonin reuptake inhibitor22 but also as an antagonist of the histamine H1 receptor, muscarinic acetylcholine receptor, and A1 adrenergic receptor.23

4.1.4. SSRIs increase oxytocin

SSRIs increase blood levels of oxytocin. It is possible that this moderates some of the antidepressant effects of SSRIs.24

4.2. Notes on serotonin reuptake inhibitors (SSRIs) in ADHD

SSRIs (serotonin reuptake inhibitors) should be used with some caution in ADHD.

4.2.1. Difference dysphoria as a regular ADHD symptom and depression to be treated

Many practitioners do not recognize dysphoria with inactivity as an original ADHD symptom, but confuse dysphoria with inactivity with dysthymia or depression and therefore improperly treat ADHD sufferers as if they had true depression.
However, dysphoria with inactivity is a functional stress symptom (the mood drop with inactivity is aimed at keeping the person active until the stressor is defeated) and is typical in ADHD. It is not a symptom of dysthymia or depression.
On the differential diagnosis of depression and dysphoria in inactivity ⇒ Depression and dysphoria in ADHD.

In practice, it has been shown that treatment with a significantly reduced amount of escitalopram (compared with use as an antidepressant) can improve dysphoric mood. Here, amounts of 2 to 5 mg a day may already be sufficient (instead of 10 to 20 as an antidepressant).
Meanwhile, a completely sufficient brightening effect is often already achieved by switching ADHD treatment from methylphenidate to amphetamine medication (Elvanse), which is therefore clearly preferable.
Unlike ADHD-HI, treatment of dysphoria with SSRIs should be avoided in ADHD-I. In ADHD-I, SSRIs should be considered only in cases of major depression.

4.2.2. SSRIs do not improve attention

Selective serotonin reuptake inhibitors, unlike stimulants, do not improve cognitive abilities. In a cohort study of n = 766,244 subjects, a relevant improvement in test scores of ADHD sufferers was found under stimulant medication. In contrast, selective serotonin reuptake inhibitors had no effect on exam scores.2526

4.2.3. SSRIs increase the activity of the DAT

Citalopram / Escitalopram appears to increase DAT activity,2728 which would be detrimental in ADHD.

A main problem of ADHD (according to this assumption mainly in ADHD-HI) is the too low dopamine level in the striatum, which is mainly caused by a too high number of dopamine transporters, which take up the released dopamine presynaptically from the synaptic cleft before it can dock postsynaptically. More active DAT therefore intensify the symptoms of ADHD.

If sleep problems also exist (as is often the case with ADHD), medications that increase serotonin levels are also said to be detrimental.29

4.2.4. SSRIs increase cortisol stress response: beneficial in ADHD-HI, detrimental in ADHD-I

Escitalopram at higher doses (20 mg), but not at 10 mg, increases the cortisol response to acute stress.2130 The same has been reported for other SSRIs 31 and for administration of the serotonin precursor tryptophan.32

Escitalopram increased anxiety at both 10 and 20 mg neither before nor during a stress test, but prolonged it thereafter.21

When treating comorbid depression in ADHD, it is imperative to be aware that increasing the cortisol response to stress may be beneficial in ADHD-HI sufferers (who often have too flat a cortisol response, which is why the HPA axis is not shut down), but may be detrimental from this standpoint in ADHD-I sufferers (who very often have an excessive cortisol response).

SSRIs cause up-regulation of mineralocorticoid and glucocorticoid receptor mRNA levels, which may restore the negative feedback regulation of the HPA axis that has broken down (despite excessive cortisol stress response) in some depression subtypes.33
In ADHD-I, this downregulation of the HPA axis is not defective.
This difference may explain why SSRIs can have a positive effect in melancholic/psychotic depression despite the inherently undesirable increase in the cortisol stress response.
In any case, as long as there is no desensitization of GR in ADHD-I without corresponding severe depression, treatment with SSRIs is not indicated.
ADHD-HI, which has a flattened cortisol stress response, is not associated with melancholic and psychotic depression but with atypical or bipolar depression, which also have a flattened cortisol stress response. Here, (lower: 2 to 5 mg) SSRI augmentation might help, especially to treat impulsivity problems.

Nevertheless, it is questionable whether the long-term effect of SSRI (escitalopram), which normalizes HPA axis activity in approximately 50% of depression sufferers, is also effective in the ADHD-I subtype.

  • The Depression League recommends SSRIs especially for atypical depression34, which, like the ADHD-HI subtype, is the externalizing stress expression form and correlates with flattened cortisol stress responses.
  • The Handbook of Psychopharmacotherapy 35 indicates that in severe (here, melancholic) depression (which, like the ADHD-I subtype, exhibits an internalizing stress phenotype with an exaggerated cortisol response to an acute stressor), treatment with tricyclic antidepressants (primarily amitryptiline and clomipramine) or SSNRIs (here, duloxetine and venlafaxine) is superior to treatment with SSRIs.3637
  • The less than optimal effect of SSRIs is further addressed in the presentation of the SSRI sertraline, which is said to work better than other SSRIs in major melancholic depression.38
  • Similarly, Ritzmann is critical of SSRIs for melancholic depression in the Swiss pharma review.39

4.2.5. SSRIs for impulsivity problems in ADHD-HI

We have been able to observe a positive effect on impulsivity problems in an individual case, as they typically occur in ADHD-HI. Impulsivity correlates neurophysiologically with low serotonin levels. Here, even a very low dose of escitalopram (2 to 5 mg - versus use as an antidepressant with 10 to 20 mg / day 40.) can contribute to a reduction in impulsivity, which may allow to lower the dosage of stimulants used in parallel.

Impulse buying, on the other hand, as occurs primarily in ADHD-I, may in our view be due to the urge for immediate reward and may be more attributable to spontaneous need satisfaction (as well as addiction) than to externalizing impulsivity induced by low serotonin levels.

4.2.6. SSRIs do not improve ADHD symptoms

In a complex double-blind study with the serotonergic antidepressant vortioxetine, no improvement in ADHD symptoms was observed after 6 weeks compared with placebo.41

The updated European consensus on the diagnosis and treatment of ADHD in adults logically concludes that SSRIs have no effective effect on ADHD.42

We know of several reports of ADHD sufferers who have taken SSRIs. None of them showed a positive effect on ADHD. Negative effects were frequently mentioned overall.

One hypothesis is that the use of SSRIs in ADHD could be improved by combining them with 5-HT1A antagonists. The authors posit that inhibitory somatodendritic 5-HT1A autoreceptors, which reduce the firing rate of 5-HT neurons, are desensitized only by long-term SSRI medication. The authors suggest that previous studies have not observed sufficiently prolonged medication and refer to pharmacologic studies in animal preparations in which SSRI effects were successfully enhanced by antagonizing the inhibitory 5-HT1A autoreceptors before administration of the SSRI fluoxetine.43
However, this hypothesis is countered by the fact that even cohort studies observing long-term medication use have found no improvement in attention with SSRIs.

5. Effect of SNRI in depression

Source with further references: Büchs.44

Serotonin and norepinephrine reuptake inhibitory antidepressants increase glucocorticoid and mineralocorticoid receptor expression and function. This leads to restoration of the impaired negative feedback of the HPA axis and normalization of its previous hyperactivity.

SSRI, SNRI, and monoamine oxidase inhibitors stimulate cortisol and ACTH directly, in both healthy and depressed individuals.
Normalization of hyperactivity of the HPA axis in depressed patients is achieved by

  • Up-regulation of mineralocorticoid and glucocorticoid receptor mRNA levels33
    • This may explain why SSRIs and SNRIs can also have a positive effect in severe (typically melancholic or psychotic) depression in ADHD-I sufferers. In melancholic and psychotic depression, GRs are desensitized. This is not the case in ADHD-I (without depression) (although likewise the cortisol stress response is exaggerated).
      More on this at Dexamethasone suppression/CRH stimulation test (DEX/CRH test)
  • Down-regulation of proopiomelanocortin mRNA expression (precursor of ACTH synthesis) in the pituitary gland
  • Attenuation of CRH gene expression and CRH mRNA synthesis in the paraventricular nucleus

The rather slow and gradual reduction of HPA axis hyperactivity by genetic mechanisms should be distinguished from the acute and direct pharmacoendocrinological effects of mirtazapine on the HPA system.45

6. Notes on tricyclic antidepressants in ADHD

Tricyclic antidepressants are considered a fifth-line treatment for ADHD-HI. Tricyclic antidepressants have a very broad-spectrum effect. They typically also act

  • Noradrenerg
    • As a noradrenaline reuptake inhibitor (quite strong)46
  • Dopaminerg
    • As a dopamine reuptake inhibitor47

Tricyclic antidepressants have demonstrated equivalent results to stimulants in numerous double-blind placebo-controlled trials in children and adults for hyperactive impulsive behavior.48495051 Combination therapy of stimulants and tricyclic antidepressants may be more effective than monotherapy, especially for hyperactivity, inattention, and oppositional symptoms, with attention to regular cardiac assessments.52

TCAs are likely to be used for nonresponding of

  • Both types of stimulants (methylphenidate and amphetamine drugs)
  • Guanfacin
  • Atomoxetine

represent a means of the fifth choice.

For comorbid anxiety, depression, and dysphoria, tricyclic antidepressants are classically helpful. For comorbid enuresis, imipramine is recommended.53

For another brief summary of studies on tricyclic antidepressants and other nonstimulants in ADHD-HI, see Budur et al 2005.54

Regular monitoring of ECG, blood pressure and pulse rate is required during treatment with tricyclic antidepressants.3

Individual tricyclic (trimipramine) and similar antidepressants (trazodone) have been shown to be highly recommended for sleep problems in ADHD. Compared to normal sleeping pills, there is no risk of dependence.

7. General information on antipsychotics for ADHD

7.1. Dopaminergic effect of antipsychotics

Neuroleptics / antipsychotics act as D2 receptor antagonists, i.e., they block the D2 receptor. However, they are not able to normalize the presynaptically increased dopamine release in psychosis / schizophrenia, but rather block the postsynaptic D2 receptor. The blockade is reversible, i.e., with a certain half-life, so that they must be taken at regular intervals. Atypical neuroleptics of the 2nd generation seem to have a blocking effect in the temporal cortex, while typicals have a blocking effect in the temporal cortex and in the striatum (Stone et al 2009).55
Secondarily, however, antipsychotics also appear to address D2 autoreceptors, stimulating dopamine release.56
This is considered an undesirable side effect in the treatment of psychosis with antipsychotics, so it is likely to be a secondary effect.

Atypical antipsychotics, in addition to blocking D2 receptors in the limbic system, are also thought to stimulate D1 receptors in the PFC, which is why they can be successful as ADHD medications in exceptional cases.57

Basically, antipsychotics / neuroleptics are not likely to be very helpful in ADHD - from a dopaminergic point of view - because they primarily aim at a reduced dopamine effect, whereas ADHD is characterized by a dopamine deficit. The benefit in ADHD would rather result from the side effect that occurs as an undesirable side effect in the treatment of psychoses.
One study found that antipsychotics are given off-label for ADHD primarily in relation to comorbid behavioral disorders, but rarely in relation to ADHD itself58

7.2. σ-Adrenergic effects of antipsychotics

Antipsychotics (D2 antagonists) are nevertheless reported to have a positive effect in ADHD at low doses, although they reduce the uptake of dopamine. The most common off-label use of antipsychotics (25%) is for ADHD.59 However, the effect (in low dosage) in ADHD is not attributed to the dopaminergic effect, but to the blockade of the σ-adrenergic receptor (antagonism), which positively stimulates the release of dopamine in the nucleus accumbens as well as dopamine uptake.606162

However, the goal of σ-adrenoceptor antagonism may be more usefully achieved with the σ-2A-adrenoceptor antagonist guanfacine, which is approved for ADHD. For more information, see Guanfacine in ADHD.

After birth, the density of D1 and D2 receptors in the striatum initially increases. The increase in D2 receptors after birth is more pronounced in males than in females.63
In adolescence, the number of these receptors drops to 40% of the initial level.64 This decrease is again significantly greater in males than in females.

Blockade of dopamine receptors increases the release of acetylcholine. Acetylcholine is partly responsible for the development of extrapyramidal symptoms.65

The more dopamine receptors are present, the greater the acetylcholinergic excess that occurs in the event of blockade of these receptors. The administration of typical antipsychotics (= typical neuroleptics, e.g. haloperidol), which block the dopamine D2 receptors as D2 antagonists, causes more pronounced acytlcholinergic side effects such as extrapyramidal symptoms (mainly disturbances of muscle tone and movement sequences) or akathisia (restlessness while sitting) in patients with a high number of dopamine receptors. The acetylcholinergic excess in individuals with a high number of dopamine receptors further explains the frequent use of anticholinergic and sedating substances and the frequent use of cocaine.66

If 70% of the dopamine receptors are occupied by cocaine (as a drug), the dopamine level in the synaptic cleft is increased and, in parallel, acetycholine release is reduced. A subjective feeling of elation results. Cocaine as well as anticholinergics cause a subjective calming in the affected persons as well as a reduction of motor restlessness and extrapyramidal symptoms due to the reduction of acetylcholinergic release. At the same time, especially with cocaine, psychotic symptoms are intensified by the dopamine excess induced by dopamine transporter blockade.66

8. Monoamine oxidase inhibitors (MAO inhibitors)

Monoamines are

  • Catecholamines
    • Dopamine
    • Norepinephrine
    • Adrenalin
  • Serotonin
  • Melatonin
  • Histamine
  • Thyronamine
  • Traceamine
    • Β-Phenylethylamine
    • Tyramine
    • Tryptamine

Monoamine oxidase (MAO) causes the degradation of monoamines by deamination.
Monoamine oxidase inhibitors reduce the degradation of monoamines and thus increase their availability.

MAO-A degrades norepinephrine and serotonin in the brain and intestine. MAO-B degrades dopamine in the brain and liver. MAO-A causes the degradation of tyrosine from food primarily in the intestine, while MAO-B causes the degradation of tyrosine in the liver. Together, they ensure that tyrosine from food is not converted to monoamines in the body.67
Tyrosine is the starting substance for the biosynthesis of DOPA, dopamine, catecholamines, melanin, thyroxine and tyramine.
Due to the peripheral tyrosine degradation effect of MAO, a low-tyrosine diet (e.g., no cheese, no red wine) must be followed when taking irreversibly acting MAO inhibitors. Otherwise, too much tyrosine would be broken down in the body and lead to excessive levels of the resulting breakdown products. Risk: among other things, heart problems.

MAO inhibitors:

  • Selegelin
    • Irreversible MOA-B inhibitor.
      Irreversible means that MAO must be re-synthesized before it can act again.
  • Moclobemide
    • Reversible selective MAO-A inhibitor.
      Reversible means that the effect is not permanent.
  • Tranylcypromine
    • Irreversible inhibitor of MAO-A and MAO-B
  • Greek mountain tea (Sideritis scardica) appears to act as an MAO inhibitor with respect to dopamine, norepinephrine, and serotonin.68

9. Medication tolerance and high sensitivity in ADHD

ADHD, according to our perception and according to the data of the ADxS symptom test, always includes high sensitivity, which can be very pronounced at times.
Highly sensitive people (even without ADHD) are more likely to react sensitively and sometimes paradoxically to medication.


  • Painkillers can
    • Not work at all
    • Already act in the smallest dosage
  • Sedatives can cause activation
  • Anesthetics can have unanticipated effects
    We have heard of cases in which anesthetics are said to be effective in significantly lower doses. There is therefore a risk of overdosage. We would be pleased if anesthesiologists could tell us about relevant experiences.
  • Caffeine can have a more intense effect (especially when taken with methylphenidate)
  • Nicotine can make you tired instead of activating
    One sufferer tells us that a ritual for falling asleep is two cigarettes or a cigarillo: after that he has 20 to 30 minutes during which he is very tired because of the nicotine and falls asleep well
  • A small dose of stimulants (1/3 to 1/2 of a single dose taken during the day) helps quite a few ADHD sufferers to fall asleep against the mind spinning

10. Cross-effects of ADHD medications

With ADH)S medications (especially tricyclic antidepressants, MAO inhibitors, and medications that address the alpha-2 adrenergic receptor), cross-effects are unfortunately common and must be considered at all costs.

A fairly comprehensive account of cross-effects in ADHD medications, as well as precautionary measures in prescribing and taking the respective preparations, can be found in Steinhausen et al.69

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  4. Hässler, Irmisch (2000): Biochemische Störungen bei Kindern mit hyperkinetischen Störungen, in Steinhausen (Hrsg.) (2000): Hyperkinetische Störungen bei Kindern, Jugendlichen und Erwachsenen, Seite 88

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  7. Liddle, Hollis, Batty, Groom, Totman, Liotti, Scerif, Liddle (2011): Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate. J Child Psychol Psychiatry. 2011 Jul;52(7):761-71. doi: 10.1111/j.1469-7610.2010.02333.x.

  8. Barkley (2014): Dr Russell Barkley on ADHD Meds and how they all work differently from each other; Youtube

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  12. Stroemer, Kent, Hulsebosch (1998): Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats; Stroke. 1998 Nov;29(11):2381-93; discussion 2393-5.

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