A Textbook of Clinical Pharmacology and Therapeutics

120 MOOD DISORDERS

Lofepramine– less sedative, and with less cardiac toxicity,
but occasionally hepatotoxic.

Mirtazapine– increases noradrenergic and serotonergic
neurotransmission via central α 2 adrenoceptors. The
increased release of 5HT stimulates 5HT 1 receptors, whilst
5HT 2 and 5HT 3 receptors are blocked. H 1 receptors are
also blocked. This combination of actions appears to be
associated with antidepressant activity, anxiolytic and
sedative effects. Reported adverse effects include increased
appetite, weight gain, drowsiness, dry mouth and (rarely)
blood dyscrasias.

Drug interactions

These include the following:

• antagonism of anti-epileptics;


• potentiation of sedation with alcohol and other central
  depressants;


• antihypertensives and diuretics increase orthostatic
  hypotension;


• hypertension and cardiac dysrhythmias with adrenaline,
  noradrenaline and ephedrine.

MONOAMINE OXIDASE INHIBITORS (MAOIs)

These drugs were little used for many years because of their
toxicity, and particularly potentially lethal food and drug inter-
actions causing hypertensive crises. Non-selective MAOIs
should only be prescribed by specialists who are experienced
in their use. They can be effective in some forms of refractory
depression and anxiety states, for which they are generally
reserved. The introduction of moclobemide, a reversible select-
ive MAO-A inhibitor, may lead to more widespread use of this
therapeutic class.
Tranylcypromineis the most hazardous MAOI because of
its stimulant activity. The non-selective MAOIs of choice are
phenelzineandisocarboxazid.

Uses

These include the following:

1. MAOIs can be used alone or (with close psychiatric
   supervision) with a TCA, in depression which has not
   responded to TCAs alone;
   2.in phobic anxiety and depression with anxiety;
   3.in patients with anxiety who have agoraphobia, panic
   attacks or multiple somatic symptoms;
   4.hypochondria and hysterical symptoms may respond well;
   5.for atypical depression with biological features such as
   hypersomnia, lethargy and hyperphagia.

Adverse effects

1. Common effects include orthostatic hypotension, weight
   gain, sexual dysfunction, headache and aggravation of
   migraine, insomnia, anticholinergic actions and oedema.
   2.Rare and potentially fatal effects include hypertensive
   crisis and 5HT syndrome, psychotic reactions,

hepatocellular necrosis, peripheral neuropathy and

convulsions.

3.Stopping a MAOI is more likely to produce a withdrawal

syndrome than is the case with tricyclics. The syndrome

includes agitation, restlessness, panic attacks and

insomnia.

Contraindications

These include the following:

• liver failure;


• cerebrovascular disease;


• phaeochromocytoma;


• porphyria;


• epilepsy.

Drug interactions

Many important interactions occur with MAOI. A treatment

card for patients should be carried at all times, which describes

precautions and lists some of the foods to be avoided. The

interactions are as follows:

• hypertensive and hyperthermic reactions sufficient to
  cause fatal subarachnoid haemorrhage, particularly with
  tranylcypromine. Such serious reactions are precipitated
  by amines, including indirectly acting sympathomimetic
  agents such as tyramine (in cheese), dopamine (in broad
  bean pods and formed from levodopa), amines formed
  from any fermentation process (e.g. in yoghurt, beer,
  wine),phenylephrine(including that administered as
  nosedrops and in cold remedies), ephedrine,amfetamine
  (all can give hypertensive reactions), other amines,
  pethidine(excitement, hyperthermia), levodopa
  (hypertension) and tricyclic, tetracyclic and bicyclic
  antidepressants (excitement, hyperpyrexia). Buspirone
  should not be used with MAOIs. Hypertensive crisis may
  be treated with α-adrenoceptor blockade analogous to
  medical treatment of patients with phaeochromocytoma
  (see Chapter 40). Interactions of this type are much less
  likely to occur with moclobemide, as its MAO inhibition
  is reversible, competitive and selective for MAO-A, so that
  MAO-B is free to deaminate biogenic amines;


• failure to metabolize drugs that are normally oxidized,
  including opioids, benzodiazepines, alcohol (reactions
  with alcoholic drinks occur mainly because of their
  tyramine content). These drugs will have an exaggerated
  and prolonged effect;


• enhanced effects of oral hypoglycaemic agents, anaesthetics,
  suxamethonium, caffeine and anticholinergics (including
  benzhexol and similar anti-Parkinsonian drugs);


• antagonism of anti-epileptics;


• enhanced hypotension with antihypertensives;


• central nervous system (CNS) excitation and hypertension
  withoxypertine(an antipsychotic) and tetrabenazine(used
  for chorea);


• increased CNS toxicity with triptans (5HT 1 agonists) and
  withsibutramine.