Coming Off Psychiatric Medication


Phenelzine, Isocarboxazid, Tranylcypromine, Moclobemide

MAOIs are generally prescribed to individuals who become depressed with 'atypical, hypochondriacal or hysterical' features, or individuals who express a fear of a specific situation/object etc. (phobia).

How the MAOI's interact with/affect the brain

The theory behind how MAOI's and other antidepressants elevate individuals mood is based around the assumption that individuals who are feeling depressed have reduced levels of a neurotransmitters, particularly serotonin and noradrenaline in the brain. Neurotransmitters are released from neurons (cells found in the brain and other parts of the nervous system) and act as messengers, passing signals between neurons. For example, when a nerve impulse arrives at a serotonergic (serotonin releasing) neuron (also known as a pre-synaptic neuron), serotonin is released from the cell and diffuses through a space between two neurons, called the synaptic cleft. Serotonin then binds to specific serotonin receptors on a different neuron (post-synaptic neuron) producing a specific signal, impulse or effect. Serotonin is then released from its receptors and 're-absorbed' into the pre-synaptic neuron, or degraded by enzymes in the synaptic cleft. It is a similar mechanism through which noradrenaline is released from a noradrenergic (noradrenaline releasing) pre-synaptic neuron, binds to noradrenaline receptors on the post-synaptic neuron and is then 're-absorbed' into the neuron it was originally released from.

Monoamine oxidase (MAO) is an enzyme present in multiple cell types and is involved in breaking down serotonin and noradrenaline and other monoamine neurotransmitters into inactive substances. It is present in all serotonergic and noradrenergic neurons and in the synaptic clefts between these neurons and the postsynaptic neurons. When a MAOI is introduced to the body, it enters neurons and binds to and inhibits the activity of MAO, leading to a reduction in the breakdown of serotonin and noradrenaline. Phenelzine, Isocarboxazid and Tranylcypromine bind to MAO permanently, therefore completely inhibiting the breakdown of noradrenaline, serotonin and other monoamines, until new MAO enzymes are synthesised. However, Moclobemide is a reversible inhibitor of MAO, so Moclobemide will temporarily inhibit the breakdown of noradrenaline, serotonin and other monoamines. In the serotonergic and noradrenergic neurons this has the effect of increasing the amounts of neurotransmitters available to be re-released. In the synaptic cleft, decreased breakdown of the neurotransmitters leads to a higher concentration of these substances and a greater chance of these substances re-attaching to a receptors on the post synaptic neuron and generating further impulses/signals.

BNF Doses

The doses listed below are the maximum safe amounts an individual theoretically could be prescribed daily. However, the usual 'therapeutic' doses will vary depending on the individual and the prescriber.

Phenelzine: Adult max = 90 mg daily

Isocarboxazid: Adult max = 60 mg daily

Tranylcypromine: Adult max = 30 mg daily

Moclobemide: Adult max = 600 mg daily

Cautions with MAOI's

Individuals prescribed MAOI's should be warned about the recommended dietary restrictions, as the combination of certain foods and MAOI's can lead to elevated blood pressure, cause individuals to have throbbing headaches and increases the risk of developing strokes. As stated earlier, MAOI's cause an accumulation of noradrenaline and serotonin and other molecules in the nerve synapses. However, the enzyme MAO is found in many body cells and noradrenaline will accumulate at these sites when an MAOI is taken. Noradrenaline serves as a pressor, and along with other molecules will have the effect of increasing an individuals blood pressure.

Individuals taking MAOI's are advised to avoid foods containing the molecule tyramine, another pressor, as ingestion of these foods along with an MAOI can lead to the development of high blood pressure. Foods to be avoided include; mature cheese, pickled herring, broad bean pods, Bovril, Oxo, Marmite or any similar meat or yeast extracts. Avoid foods that are stale or in danger of 'going off', this includes meat, fish, poultry and game should be avoided. Alcohol or low alcoholised drinks should also be avoided. Certain 'over the counter' medications including cough and decongestant preparations should also be avoided as their main ingredients are pressor molecules.

Side effects of MAOIs

Common side-effects include; postural hypotension (low blood pressure upon standing, which may lead individuals to faint) and dizziness.

Less common side-effects include; drowsiness, insomnia, headache, weakness and fatigue, dry mouth, constipation. Agitation, tremors, nervousness, euphoria, arrhythmias, blurred vision, difficulty passing water, sweating, convulsions, rashes, low white blood cell counts, sexual disturbances and weight gain with inappropriate appetite. Psychotic episodes with hypomanic behaviour, confusions and hallucinations may be induced in susceptible individuals.

Rarely; individuals have developed fatal progressive hepatocellular necrosis (serious liver damage!), paraesthesia (spontaneously occurring abnormal tingling sensations), peripheral neuropathy (malfunction/damage to the nerves in the arms and legs, usually feels like weakness or numbness in affected limbs).

Drug specific side-effects

Phenelzine ' Liver damage more frequent than with Tranylcypromine

Tranylcypromine ' More frequently than the other MAOI'S, individuals report throbbing headaches and develop high blood pressure Moclobemide ' sleep disturbances, headaches, restlessness, gastrointestinal disorders, oedema (swellings due to retention of fluid), skin reactions, confusional states. Rarely, galactorrhoea (milk secretion from the breasts) and raised liver enzymes (suggesting liver damage or abnormal liver function).

There may be other side-effects of taking MAOI's which are not listed above, those listed are just the more commonly seen side-effects or the acknowledged ones.


When discussing coming off psychiatric drugs the terms withdrawal and discontinuation will be used interchangeably. Although the term withdrawal is usually associated with coming off drugs to which an individual is addicted to, when an individual comes off MAOI's they are not addicted to the drug, they do not consciously crave the drug. The effects an individual may experience when withdrawing/discontinuing/reducing a MAOI are not related to addiction but rather to the body struggling to adapt to the absence of a chemical it has become used to being present.

Withdrawal effects

The effects listed below are taken from cases reports of individuals who have abruptly discontinued taking a MAOI. However, as you will read later it is recommended that when attempting to come off a MAOI the dose should be gradually reduced over a period of time, rather than all at once in order to try to prevent developing withdrawal effects. ' Agitation ' Irritability ' Pressured speech ' Insomnia and nightmares ' Visual, olfactory, and tactile hallucinations ' Feelings of disorientation to time and place ' Paranoia ' Aggressiveness ' Slurred speech ' Myoclonic jerks (sudden spasm of muscles) ' Clonus (rhythmical contraction of muscle in response to a suddenly applied and then sustained stretch stimulus) ' Ataxia (unsteady gait and balance) ' Athetosis (a writhing involuntary movement especially affecting the hands, face and tongue) ' Catatonia (a state in which an individual becomes mute or stuporous or adopts unusual postures) ' Electric shock feelings

If a symptom is due to withdrawal of a drug, it will typically occur soon after a reduction (or discontinuation) of the drug and disappear within about 2 weeks (and generally not persist beyond 3 weeks).

Rates of withdrawal

All of the above withdrawal symptoms occurred in individuals who abruptly discontinued their MAOI, therefore the first point to make is that a slow gradual discontinuation of the MAOI is probably the safest way to avoid developing withdrawal effects. There are currently no guidelines in existence as to how long or at what rate an individual should withdraw from a MAOI. Making 10% reductions in the dose every 2 weeks should allow for a slow enough rate so that the brain has time to adapt to the reduced levels of the MAOI and avoid unwanted withdrawal effects. The limited literature on MAOI withdrawal may reflect the fact that most individuals do not develop significant problems when withdrawing from the MAOI, if the doses are reduced slowly over a period of time. As with withdrawal from any psychiatric medication, the longer an individual has been on a drug, it would be more sensible to reduce over a longer period of time. Example /So if an individual was taking 50mg Phenelzine a day and wanted to reduce the drug by 10% every two weeks, the first 2 weeks they would take 45mg per day, the next 2 weeks 40mg per day etc. Approximately 5 months later they would have fully come off the drug. However, if after 4 weeks they found that they were developing withdrawal effects it would perhaps be sensible to avoid further reductions until they no longer felt the withdrawal effects and if they felt the need to increase the dose by 10% until the withdrawal effects subsided they did this. Also, they could decide to reduce in 5% steps from that point on rather than the original 10% steps to further avoid developing unpleasant withdrawal effects./ Even if you are not successful in coming off your medication at the first attempt you will probably learn from the experience, what was beneficial, what could you have done differently and ultimately had an opportunity to evaluate the role of the drug in your life.


If you are taking any medications other than your psychiatric drugs it is worthwhile speaking to your GP about what potential interactions your psychiatric medications may have with your other medications.