Monoamine oxidase withdrawal

Berlin, I., Spreux-Varoquaux, O., Said, S., Launay, 1. Effects of past history of major depression on smoking characteristics, monoamine oxidase-A and -B activities and withdrawal symptoms in dependent smokers. Drug Alcohol Depend. 45 31, 1997. 

Drug withdrawal reactions - tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, barbiturates, alcohol, opioids. 

Like the benzodiazepines, buspirone appears to be safe even when given in very high doses. The most common side effects are dizziness, light-headedness, and headache. Abuse, dependence, and withdrawal have not been reported, and buspirone administration does not produce any cross-tolerance to the benzodiazepines. Buspirone has been reported to increase blood pressure in patients taking monoamine oxidase inhibitors, and it may increase plasma levels of haloperidol if coadministered with that agent. 

Bhattacharya SK, Glover V, Sandler M, et al Raised endogenous monoamine oxidase inhibitor output in post withdrawal alcoholics effects of L-dopa and ethanol. Biol Psychiatry 17 687-694, 1982... 

The enzyme found in the liver will deaminate secondary and tertiary aliphatic amines as well as primary amines, although the latter are the preferred substrates and are deaminated faster. Secondary and tertiary amines are preferentially dealky la ted to primary amines. For aromatic amines, such as benzylamine, electron-withdrawing substituents on the ring will increase the reaction rate. The product of the reaction is an aldehyde (Fig. 4.30). Amines such as amphetamine are not substrates, seemingly due to the presence of a methyl group on the a-carbon atom (Fig. 4.27). Monoamine oxidase is important in the metabolic activation and subsequent toxicity of allylamine (Fig. 4.31), which is highly toxic to the heart. The presence of the amine oxidase in heart tissue allows metabolism to the toxic metabolite, allyl aldehyde (Fig. 4.31). Another example is the metabolism of MPTP to a toxic metabolite by monoamine oxidase in the central nervous system, which is discussed in more detail in chapter 7. 

Most antidepressants decrease the quantity of REM sleep in the depressed patient, although it is difficult to say whether this is a reflection of the action of the drugs or due to the underlying pathology. Abrupt withdrawal of antidepressants, particularly the monoamine oxidase inhibitors, is often associated with REM rebound. 

The older tricyclic antidepressants and monoamine oxidase inhibitors also cause withdrawal mania and a variety of other adverse withdrawal effects, including cognitive and emotional disturbances and psychosis. Many of them have strong anticholinergic effects and therefore produce severe anticholinergic rebound on withdrawal, including cardiovascular and gastrointestinal symptoms. I have seen patients who have taken tricyclics for many years and then been unable to withdraw from them. 

The problem of the long half-life of fluoxetine, leading to interactions with monoamine oxidase inhibitors, even after withdrawal, has been discussed previously (SEDA-13, 12), and caused the manufacturer to circulate a warning to that effect. 

Tyrer P. Clinical effects of abrupt withdrawal from tricyclic antidepressants and monoamine oxidase inhibitors after long-term treatment. J Affect Disord 1984 6(l) l-7. 

Anorectic drugs act mainly on the satiety centre in the hypothalamus (1). They also have metabohc effects involving fat and carbohydrate metaboUsm. Most of them are structurally related to amfetamine and increase physical activity. Their therapeutic effect tends to abate after some months, and part of this reduction in effect may be due to chemical alterations in the brain. Fenfluramine commonly produces drowsiness in normal doses, but has stimulaut effects in overdosage. Dexamfetamine, phenmetrazine, and benzfetamine all tend to cause euphoria, with a risk of addiction. Euphoria occasionally occurs with amfepramone (diethylpropion), phentermine, and chlorphentermine, but to a much lesser extent. Some adverse effects are due to sympathetic stimulation and gastrointestinal irritation these may necessitate withdrawal but are never serious. There are interactions with monoamine oxidase inhibitors and antihypertensive drugs. 

Clonidine withdrawal may result in an excess of circulating catecholamines. Therefore, caution should be exercised in concomitant use of drugs which effect the metabolism or tissue uptake of these amines (monoamine oxidase inhibitors or tricyclic antidepressants, respectively) (1). 

Nervous system Seizures have been attributed to flumazenil [104, 105, 106, 107, 108, 109, 110, 111 ], including status epilepticus [112, 113 ], which can be fatal. However, it has been suggested that seizures are not a toxic effect of flumazenil, but are in many cases instead due to unmasking of the anticonvulsant effect of the benzodiazepine or to a severe benzodiazepine-withdrawal syndrome furthermore, in some cases they may be due to other drugs taken at the same time, such as tricyclic antidepressants [1143]. Thus, it has been recommended that flumazenil should not be given to patients who have used benzodiazepines for seizure disorders or to patients who have taken other drugs that increase the risk of seizures (e.g. bupropion, ciclosporin, cocaine, cyclic antidepressants, isoniazid, lithium, methylxanthines, monoamine oxidase inhibitors, and propoxyphene). 

Rose JE, Behm FM, Ramsey C, Ritchie JRJC. Platelet monoamine oxidase, smoking cessation and tobacco withdrawal symptoms. Nicotine and Tobacco Res. 2001 3(4) 383-390. 

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