All medications described should only ever be prescribed by experienced doctors. Our explanations are only intended as an impetus for a personal consultation with a doctor.
As the ADHD symptoms originate predominantly from the dopaminergic and noradrenergic systems, combined medication with dopaminergic and noradrenergic agents is recommended.
Unfortunately, medication for ADHD does not work in a curative way. They merely correct the neuronal malfunctions - like glasses that correct an existing visual defect as long as they are worn.
1. Medication affecting stress response¶
By influencing the stress response, we do not mean sedative or other general effects, but effects of medication on the response of the stress regulation systems.
1.1. Anxiolytics¶
Anxiolytics (anti-anxiety medication) generally reduce the reactivity of the stress systems even when administered individually.
1.2. Antidepressants¶
Single doses of antidepressants have partly inhibiting and partly activating effects on the stress systems.
1.3. Stimulants¶
A stimulating effect alone is not sufficient to be effective in ADHD. Although pseudoephedrine and ephedrine are stimulants, they are ineffective for ADHD. Furthermore, L-methylphenidate is 6 times more stimulating than D-MPH, yet only D-MPH is effective for ADHD
1.3.1. Stimulants and stress resistance¶
Stimulants stimulate the reactivity of the stress systems.
Stimulants are able to align the attentional control of persons with ADHD with that of people without ADHD by increasing their motivational capacity. This could (partly) explain why stimulants are just as helpful in ADHD-HI and ADHD-C as in ADHD-I. More on the deviant function of the DMN in ADHD and its normalization by stimulants, including further references at ⇒ DMN (Default Mode Network) In the article ⇒ Neurophysiological correlates of hyperactivity.
1.3.2. Stimulants and emotions¶
Barkley 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) is inhibited. This naturally reduces emotions.
Too high a dosage of stimulants therefore leads to restricted emotions.
He goes on to report that for this reason mixed medication is being used more and more frequently in order to preserve the great advantage of stimulants and limit the disadvantages.
1.3.3. Long-term compliance - phases of medication intake¶
It is often observed that stimulants are discontinued by people with ADHD a few years (approx. 1.5 to 3 years) after the initial prescription. A few years later (around 4 to 6 years after the initial prescription), increased use occurs again.
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. More on this at ⇒ Neurophysiological correlates of learning problems in ADHD.
Taking stimulants now makes it possible to adapt functional behavior to the current requirements.
If this adaptation has occurred sufficiently after a few years, a short-term discontinuation of stimulants does not lead to immediate deficits in behavior, as the currently stored behavioral patterns are now adapted to the current environment and therefore continue to function for the moment even without medication.
However, if the patient continues not to take the medication, the constantly necessary adaptation of behavioral patterns to new environmental requirements does not take place. As the environmental requirements gradually change, the stored behaviours that were optimized for earlier environmental requirements become increasingly dysfunctional. Once the difficulties have reached a certain level again, the psychological stress reminds the patient that the medication helped very well against these difficulties in the beginning, which leads to a renewed intake of medication.
The self-reported reasons for discontinuing medication are often a distrust of medication among parents (concern about side effects, weight loss, growth retardation), while young people with ADHD themselves state completely different motives, namely the desire to develop freely without medication.
2. Dopaminergic drugs¶
Dopaminergic drugs have the leading role in ADHD, as most symptoms are caused by dopamine (action) deficiency in the dlPFC and striatum.
In addition to psychotherapeutic measures, dopaminergic drugs have the further benefit that they increase the neuroplasticity of the brain and thus support the effectiveness of therapy or establish a therapeutic capability.
Around 5 % of dopamine is metabolized into noradrenaline, so that dopaminergic drugs always have an (albeit minor) noradrenergic influence at the same time.
Dopaminergic drugs address the anterior attention center.
⇒ The dopaminergic and the noradrenergic attention center.
3. Noradrenergic drugs¶
Noradrenaline is formed in the nucleus coeruleus and controls, among other things, the posterior attention center in the parietal cortex.
⇒ The dopaminergic and the noradrenergic attention center.
3.1. Drugs that increase noradrenaline levels¶
Noradrenaline reuptake inhibitors increase the amount of noradrenaline available. Pure noradrenaline reuptake inhibitors are the “second choice” alongside dopaminergic and noradrenergic stimulants. However, they can support medication with MPH if necessary.
MPH, amphetamine drugs and atomoxetine each have a dopaminergic and noradrenergic effect, whereby atomoxetine only has a noradrenergic and dopaminergic effect in the PFC, while MPH also has a dopaminergic effect in the striatum.
⇒ Effect of atomoxetine different from MPH
3.2. Effect of noradrenergic drugs¶
The effect of noradrenergic medication is subjectively described by people with ADHD as increasing the “green zone” between underchallenge (which causes people with ADHD to switch off internally) and overload (which drives people with ADHD into stress). The balance increases. Affective outbursts (outbursts of anger, emotional overreactions) are reduced.
Noradrenergic medication improves ADHD symptoms
- Affective outbursts (outbursts of anger)
- Emotional impulse control
- Alertness
-
Vigilance
Dopaminergic drugs cannot directly influence these symptoms (at most through noradrenaline, which is produced from the breakdown of dopamine).
Amphetamine medication is also said to be helpful here.
An augmenting optimal setting with noradrenergic medication can subjectively double the gain that methylphenidate brings. (Individual) persons with ADHD report that an optimally adjusted dosage in combination with stimulants completely eliminated the symptoms of ADHD in them. Unfortunately, this effect was limited in time, which indicates an up- or downregulation of receptors (see 2.4.).
3.3. Response speed of noradrenergic drugs¶
Primary noradrenergic drugs usually need to be flooded for 2 to 3 weeks before they take effect.
Noradrenergic medication should be discontinued gradually over the same period of time in order to avoid depression.
Due to the slow dosing response, noradrenergic medication should not be increased, omitted or discontinued in the short term.
The response speed corresponds to that of serotonin reuptake-inhibiting drugs.
3.4. Long-term effect of noradrenergic drugs problematic¶
The effect of noradrenergic drugs can wear off somewhat after a while (unlike that of stimulants).
We suspect that most noradrenergic drugs have a tonic effect, i.e. cause a long-term increase in NE levels. However, ADHD symptoms only improve with a phasically increased noradrenaline level. A tonically increased NE level is actually counterproductive.
Many people with ADHD have noticed 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. Individual people with ADHD have also reported this as an individual reaction to atomoxetine.
Scheidtmann then goes on to point out that noradrenergic drugs (e.g. antidepressants) do not help with motor rehabilitation if they are used as long-term medication, as tricyclic antidepressants permanently stimulate the noradrenergic receptors and this leads to a loss of receptor sensitivity (especially with regard to learning processes).
This is consistent with the experience of using noradrenergic tricyclic antidepressants for ADHD. It is often reported that there is a very good response at the beginning, but that this diminishes with continued medication.
While dopaminergic medications can be discontinued or increased for a short period of time as required without any problems, this should be avoided with noradrenergic medications. Noradrenergic medication carries the risk of depression in the event of overdose and sudden fluctuations in dosage.
A clearly structured daily routine, in which activity and breaks alternate sensibly, should train the noradrenergic system and help to normalize the production of noradrenaline.
3.5. Contraindications¶
Benzodiazepines reduce the activity of the locus coeruleus And thus reduce the production and transport of noradrenaline to other parts of the brain. They should therefore be contraindicated in ADHD in general. Surprisingly, however, they are helpful in the short term: however, they should not be prescribed due to their massive dependency potential, which occurs after just 14 days at normal doses. MPH and amphetamine drugs, on the other hand, have no dependency potential.
There are also other side effects and interactions.
4. Serotonergic medication¶
4.1. General information on SSRIs¶
4.1.1. Response speed of serotonergic drugs¶
Although serotonin levels are altered by serotonergic drugs in the very short term, serotonergic drugs usually have to be taken for 2 to 3 weeks before they take effect. It can therefore 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 longer, the inhibitory serotonin autoreceptors are desensitized, which reduces their inhibitory influence. This increases serotonergic neurotransmission. As the desensitization of the serotonin-1 autoreceptors takes time, the onset of action is delayed to this extent.
Adaptive down- or upregulation of receptor systems or neuroplastic processes are assumed to be further mechanisms of action.
Serotonergic medication should be discontinued gradually over at least the same period of time in order to avoid side effects. According to other reports, discontinuation of serotonergic medication can last up to six months. We now have a large number of reports from people with ADHD who have had little benefit from antidepressant medication, but who have suffered massive side effects, especially when discontinuing antidepressants, which have exceeded the side effects of ADHD medication many times over in terms of severity.
Due to the slow dosage response, serotonergic medication should not be increased, omitted or discontinued at short notice.
4.1.2. SSRIs and σ-receptors¶
SSRI sorted by binding strength to the σ1 receptor in descending order:
- Fluvoxamine
- Less affine, but highly selective on the serotonin transporter
- Sigma-1 agonist
- Removes cognitive deficits typical of depression
- Improves psychotic symptoms
- Enhances nerve growth factor-induced neurite outgrowth in PC12 cells
- Sertraline
- Sigma-1 antagonist
- Removes cognitive deficits typical of depression
- Worsens psychotic symptoms
- Reduces nerve growth factor-induced neurite outgrowth in PC12 cells
- Fluoxetine
- Citalopram
- Escitalopram is the active S-enantiomer of the racemic citalopram.
- Paroxetine (almost no binding at all)
- Paroxetine also has an anticholinergic effect
can cause concentration problems and forgetfulness
4.1.3. Single-dose SSRIs increase anxiety and risk of panic attacks¶
Single doses of escitalopram increase the risk of panic attacks. Anxiety and tension were also increased by a single dose of chlorimipramine/chloromipramine/clomipramine, a tricyclic antidepressant that acts primarily as a serotonin reuptake inhibitor but also as an antagonist of the histamine H1 receptor, the muscarinic acetylcholine receptor and the A1 adrenoceptor.
4.1.4. SSRIs increase oxytocin¶
SSRIs increase the blood level of oxytocin. This may moderate some of the antidepressant effects of SSRIs.
4.2. Notes on serotonin reuptake inhibitors (SSRIs) for ADHD¶
SSRIs (serotonin reuptake inhibitors) should be used with some caution in ADHD.
4.2.1. Difference between 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 people with ADHD as if they had real depression.
However, dysphoria during inactivity is a functional stress symptom (the mood drop during inactivity is aimed at keeping the person with ADHD active until the stressor is defeated) and is typical in ADHD. It is not a symptom of dysthymia or depression.
Differential diagnosis of depression and dysphoria with inactivity ⇒ Depression and dysphoria in ADHD.
In practice, it has been shown that treatment with a significantly reduced amount of escitalopram (compared to its use as an antidepressant) can improve dysphoric mood. Here, quantities of 2 to 5 mg per day may already be sufficient (instead of 10 to 20 as an antidepressant).
However, switching ADHD treatment from methylphenidate to amphetamine medication (Vyvanse) often has a completely sufficient brightening effect, which is therefore clearly preferable.
In contrast to ADHD-HI, treatment of dysphoria with SSRIs should be avoided in ADHD-I. In ADHD-I, SSRIs should only be considered in cases of severe depression.
4.2.2. SSRIs do not improve attention¶
In contrast to stimulants, selective serotonin reuptake inhibitors do not improve cognitive abilities. In a cohort study of n = 766,244 subjects, a relevant improvement in exam results of people with ADHD was found under stimulant medication. In contrast, selective serotonin reuptake inhibitors had no effect on examination results.
4.2.3. SSRIs increase the activity of the DAT¶
Citalopram / escitalopram appears to increase the activity of the DAT, which would be detrimental in ADHD.
One of the main problems of ADHD (according to this assumption, primarily in ADHD-HI) is the low dopamine level in the striatum, which is mainly caused by an excessive number of dopamine transporters that 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 there are also sleep problems (as is often the case with ADHD), drugs that increase serotonin levels are also said to be detrimental.
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. The same has been reported for other SSRIs and for the administration of the serotonin precursor tryptophan.
Escitalopram at 10 and 20 mg did not increase anxiety either before or during a stress test, but prolonged it afterwards.
When treating comorbid depression in ADHD, it is important to be aware that increasing the cortisol response to stress can be beneficial in people with ADHD-HI (who often have an excessively flat cortisol response, which is why the HPA axis is not switched off), but can be detrimental from this point of view in people with ADHD-I (who very often have an excessive cortisol response).
SSRIs cause an up-regulation of mineralocorticoid and glucocorticoid receptor mRNA levels, which can restore the negative feedback regulation of the HPA axis that has broken down in some depression subtypes (despite an excessive cortisol stress response).
In ADHD-I, this downregulation of the HPA axis is not defective.
This difference could explain why SSRIs can have a positive effect in melancholic / psychotic depression despite the undesirable increase in the cortisol stress response.
As long as there is no desensitization of the GR in ADHD-I without correspondingly severe depression, treatment with SSRIs is not indicated in any case.
ADHD-HI, which has a flattened cortisol stress response, is not associated with melancholic and psychotic, but with atypical or bipolar depression, which also have a flattened cortisol stress response. Here, (lower: 2 to 5 mg) SSRI augmentation could help, especially for the treatment of impulsivity problems.
Nevertheless, it is questionable whether the long-term effect of SSRIs (escitalopram), which normalizes the activity of the HPA axis in around 50% of people with ADHD, is also effective in the ADHD-I subtype.
- The Depression League recommends SSRIs especially for atypical depression, which, like the ADHD-HI subtype, represents the externalizing form of stress expression and correlates with a flattened cortisol stress response.
- The Handbook of Psychopharmacotherapy points out that treatment with tricyclic antidepressants (primarily amitryptiline and clomipramine) or SSNRIs (here duloxetine and venlafaxine) is superior to treatment with SSRIs in severe (here: melancholic) depression (which, like the ADHD-I subtype, shows an internalizing stress phenotype with an exaggerated cortisol response to an acute stressor).
- The suboptimal effect of SSRIs is also discussed in the presentation of the SSRI sertraline, which is said to work better than other SSRIs in severe melancholic depression.
- Ritzmann is also critical of SSRIs for melancholic depression in the Swiss pharma review.
4.2.5. SSRIs for impulsivity problems in ADHD-HI¶
In one individual case, we were able to observe a positive effect on impulsivity problems, which typically occur in ADHD-HI. Impulsivity correlates neurophysiologically with a low serotonin level. Here, even a very low dose of escitalopram (2 to 5 mg - compared to use as an antidepressant with 10 to 20 mg / day .) can contribute to a reduction in impulsivity, which may allow the dosage of the stimulants used in parallel to be reduced.
In contrast, we believe that impulse buying, which occurs predominantly in ADHD-I, may be due to the urge for immediate reward rather than externalizing impulsivity induced by low serotonin levels and may be due to spontaneous need satisfaction (as well as addiction).
4.2.6. SSRIs do not improve ADHD symptoms¶
SSRIs showed no effect in ADHD
In an elaborate double-blind study with the serotonergic antidepressant vortioxetine, no improvement in ADHD symptoms was found after 6 weeks compared to placebo.
The updated European consensus on the diagnosis and treatment of ADHD in adults consistently concludes that SSRIs have no effective effect on ADHD.
We know of several reports of people with ADHD who have taken SSRIs. None of them showed a positive effect on ADHD. Overall negative effects were frequently mentioned.
Particularly disadvantageous are the duration of several weeks until any (antidepressant) effect occurs and, even more so, the sometimes considerable dosing side effects, some of which require very slow dosing (especially with venlaflaxine).
One hypothesis is that the use of SSRIs in ADHD could be improved by a combination with 5-HT1A antagonists. The authors state that the inhibitory somatodendritic 5-HT1A autoreceptors, which reduce the firing rate of 5-HT neurons, are only desensitized by long-term SSRI medication. The authors assume that the previous studies have not observed sufficiently long medication and refer to pharmacological studies on animal preparations in which the effect of SSRI was successfully improved by antagonizing the inhibitory 5-HT1A autoreceptors prior to the administration of the SSRI fluoxetine.
However, this hypothesis is contradicted by the fact that even cohort studies that observe long-term use of medication have not found any improvement in attention with SSRIs.
4.2.6. SSRIs and stimulants: risk of serotonin syndrome¶
A combination of SSRIs and stimulants should be handled with caution in view of the risk of serotonin syndrome
However, the serotonergic effect of stimulants is limited with normal doses of medication.
Serotonin syndrome can be caused by an overdose of serotonergic drugs, by a combination of several serotonergic drugs, by metabolic cross-effects or by cross-effects with opioids. It usually becomes noticeable within 24 hours and usually subsides 24 hours after discontinuation of the triggering medication.
Symptom severity can vary greatly.
Possible symptoms:
- Fear
- Restlessness / Restlessness
- Jumpiness
- Delirium with confusion
- Somnolence
- Trembling / muscle spasms / muscle twitching
- Muscle rigidity / seizures
- Clonus (successive reflexive muscle contractions following a stretching stimulus)
- rapid heartbeat
- High blood pressure
- high body temperature
- Sweating
- Chills
- Vomiting
- Diarrhea
- Abdominal pain
5. Effect of SNRIs on depression¶
Source with further references: Büchs.
Antidepressants that inhibit serotonin and noradrenaline reuptake increase glucocorticoid and mineralocorticoid receptor expression and function. This leads to a restoration of the disturbed negative feedback of the HPA axis and the normalization of its previous hyperactivity.
SSRI, SNRI and monoamine oxidase inhibitors directly stimulate cortisol and ACTH in both healthy and depressed people.
Normalization of the hyperactivity of the HPA axis in depressive patients is achieved by
- Up-regulation of mineralocorticoid and glucocorticoid receptor mRNA levels
- This could explain why SSRIs and SNRIs can also have a positive effect in severe (typically melancholic or psychotic) depression in people with ADHD-I. In melancholic and psychotic depression, the GR are desensitized. This is not the case with ADHD-I (without depression) (although the cortisol stress response is also excessive).
Find out more 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 the hyperactivity of the HPA axis by genetic mechanisms must be distinguished from the acute and direct pharmacoendocrinological effects of mirtazapine on the HPA system.
6. Notes on tricyclic antidepressants for ADHD¶
Tricyclic antidepressants are considered the fifth choice of medication for ADHD-HI. Tricyclic antidepressants have a very broad-spectrum effect. They typically also have the following effects
-
Noradrenergic
- As a noradrenaline reuptake inhibitor (quite strong)
-
Dopaminergic
- As a dopamine reuptake inhibitor
Tricyclic antidepressants have shown equivalent results to stimulants in numerous double-blind placebo-controlled studies in children and adults with regard to hyperactive impulsive behavior. Combination therapy of stimulants and tricyclic antidepressants may be more effective than monotherapy, especially for hyperactivity, inattention and oppositional symptoms, with attention paid to regular cardiologic testing.
TCAs are likely to be used for non-responding
- Both types of stimulants (methylphenidate and amphetamine drugs)
- Guanfacine
- Atomoxetine
represent a fifth choice of medication.
For comorbid anxiety, depression and dysphoria, tricyclic antidepressants are classically helpful. Imipramine is recommended for comorbid enuresis.
For another brief summary of studies on tricyclic antidepressants and other non-stimulants in ADHD-HI, see Budur et al 2005.
Regular monitoring of ECG, blood pressure and pulse rate is necessary during treatment with tricyclic antidepressants.
Individual tricyclic (trimipramine) and similar antidepressants (trazodone) have been shown to be highly recommended for sleep problems in ADHD. There is no risk of dependence compared to normal sleeping pills.
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 release of dopamine in psychosis/schizophrenia, but rather block the postsynaptic D2 receptor. The blockade is reversible, i.e. it has a certain half-life, so that it must be taken at regular intervals. Atypical 2nd generation neuroleptics appear to have a blocking effect in the temporal cortex, while typical drugs have a blocking effect in the temporal cortex and the striatum (Stone et al 2009).
Secondarily, however, antipsychotics also appear to address D2 autoreceptors, which stimulates the release of dopamine
This is considered an undesirable side effect in the treatment of psychoses with antipsychotics, so that a secondary effect can be assumed.
In addition to blocking D2 receptors in the limbic system, atypical antipsychotics are also said to stimulate D1 receptors in the PFC, which is why they can be successful as ADHD medication in exceptional cases.
In principle, antipsychotics / neuroleptics are unlikely to be helpful in ADHD from a dopaminergic perspective, as they primarily aim to reduce the 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 for ADHD are given off-label primarily in relation to comorbid behavioral disorders, but barely in relation to ADHD itself
7.2. σ-Adrenergic effect of antipsychotics¶
Antipsychotics (D2 antagonists) are nevertheless said to have a positive effect on ADHD at low doses, although they reduce the absorption of dopamine. The most common off-label use of antipsychotics (25 %) is for ADHD. However, the effect (at low doses) 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 and dopaminergic uptake.
However, the goal of σ-adrenoceptor antagonism is more likely to be achieved with the σ-2A-adrenoceptor antagonist guanfacine, which is approved for ADHD. See also under Guanfacine for AD(H)S.
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 men than in women.
In adolescence, the number of these receptors falls to 40% of the initial level. This decrease is again significantly greater in men than in women.
Blocking dopamine receptors increases the release of acetylcholine. Acetylcholine is partly responsible for the development of extrapyramidal symptoms.
The more dopamine receptors are present, the greater the acetylcholinergic excess that occurs when these receptors are blocked. The administration of typical antipsychotics (= typical neuroleptics, e.g. haloperidol), which block the dopamine D2 receptors as D2 antagonists, causes more pronounced acetylcholinergic side effects such as extrapyramidal symptoms (primarily disorders of muscle tone and movement sequences) or akathisia (restlessness) in people with ADHD with a high number of dopamine receptors. The acetylcholinergic excess in persons with ADHD with a high number of dopamine receptors further explains the frequent consumption of anticholinergic and sedative substances as well as the frequent use of cocaine.
If 70% of the dopamine receptors are occupied by cocaine (as a drug), the dopamine level in the synaptic cleft is increased and the release of acetylcholine is reduced at the same time. The result is a subjective feeling of elation. Both cocaine and anticholinergics cause subjective calming in people with ADHD, as well as a reduction in motor restlessness and extrapyramidal symptoms due to the reduction in acetylcholinergic release. At the same time, especially with cocaine, the excess dopamine induced by dopamine transporter blockade intensifies psychotic symptoms.
8. Monoamine oxidase inhibitors (MAO inhibitors)¶
Monoamines are
-
Catecholamines
-
Dopamine
- Noradrenaline
- Adrenalin
- Serotonin
- Melatonin
- Histamine
- Thyronamine
- Traceamine
- Β-Phenylethylamine
- Tyramine
- Tryptamine
Monoamine oxidase (MAO) causes the breakdown of monoamines by deamination.
Monoamine oxidase inhibitors reduce the breakdown of monoamines and thus increase their availability.
MAO-A breaks down noradrenaline and serotonin in the brain and intestines. MAO-B breaks down dopamine in the brain and liver. MAO-A causes the breakdown of tyrosine from food primarily in the intestine, while MAO-B breaks down tyrosine in the liver. Together they ensure that tyrosine from food is not converted into monoamines in the body.
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 irreversible MAO inhibitors. Otherwise, too much tyrosine would be broken down in the body and lead to excessive levels of the resulting breakdown products. Risk: including heart problems.
MAO inhibitors:
- Selegelin
- Irreversible MOA-B inhibitor.
Irreversible means that MAO must first be re-synthesized before it can work 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 in relation to dopamine, noradrenaline and serotonin.
9. Medication tolerance and high sensitivity in ADHD¶
According to our perception and the data from the ADxS symptom test, ADHD always includes high sensitivity, which can sometimes be very pronounced.
Highly sensitive people (even without ADHD) often react sensitively and sometimes paradoxically to medication.
Examples:
- Painkillers can
- Do not work at all
- Are effective even at very low doses
- Sedatives can cause activation
- Anesthetics can have unforeseen effects
We have heard of cases in which anesthetics are said to work at significantly lower doses. There is therefore a risk of overdosing. We would be pleased if anesthesiologists could tell us about their relevant experiences.
- Caffeine can have a more intensive effect (especially when taking methylphenidate)
- Nicotine can make you tired instead of activating you
One person with ADHD tells us that a bedtime ritual is two cigarettes or a cigarillo: afterwards he has 20 to 30 minutes during which he is very tired due to the nicotine and can fall asleep well
- A small dose of stimulants (1/3 to 1/2 of a single dose taken during the day) helps many people with ADHD to fall asleep against the racing thoughts
10. Cross-effects of ADHD medication¶
With ADHD)S drugs (especially tricyclic antidepressants, MAO inhibitors and drugs that address the alpha-2-adrenoceptor), cross-effects are unfortunately common and must be taken into account.
One cross-effect of stimulants that receives far too little attention concerns caffeine. Around half of all people with ADHD suffer cross-effects when taking stimulants with caffeine, which can feel like a stimulant overdose or like significant stimulant side effects, even if caffeine alone was previously tolerated without any problems. Therefore, when dosing stimulants, caffeine should be consistently avoided. Once dosing has been completed, caffeine is less dangerous, even if the cross-effects are the same, because the cross-effects can then be easily attributed to caffeine. People with ADHD who report that they “cannot tolerate” stimulants and have not consistently omitted caffeine during dosing should consider a new - slow - dosing without caffeine.
A fairly comprehensive description of the cross-effects of ADHD medications and precautionary measures when prescribing and taking the respective preparations can be found in Steinhausen et al.
