A Textbook of Clinical Pharmacology and Therapeutics

DEPRESSIVEILLNESSES ANDANTIDEPRESSANTS 117

e.g. interpersonal difficulties or other life stresses (including
physical illness), antidepressant drugs may be useful. Drugs
used in the initial treatment of depression include TCAs and
related drugs, SSRIs and SNRIs. Although clinical experience
is most extensive with the TCAs, the side-effect profile of the
SSRIs is usually less troublesome, and these drugs are safer in
overdose. Therefore many psychiatrists and general practi-
tioners use SSRIs rather than TCAs as first-line treatment for
depression. SSRIs are more expensive than TCAs. The relative
side effects of the different antidepressant drugs are summar-
ized in Table 20.1.
In refractory depression, other drug treatment or electro-
convulsive therapy (ECT) are considered. Alternative drug
strategies include (1) adding lithiumto a tricyclic to give a
lithiumblood level of 0.6–0.8 mmol/L; (2) combining anti-
depressants; (3) augmenting with T3 (or T4), a mood stabilizer
such as lamotrigine,buspironeorestradiol; (4) MAOIs, usu-
ally prescribed only by psychiatrists; (5) MAOI plus a TCA –
but only in expert psychiatric hands; or (6) small doses of flu-
pentixol(for short-term treatment only).
Figures 20.1 and 20.2 show a treatment algorithm for man-
agement of depressive illness.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS
(SSRIs)

These drugs are safer in overdose than the tricyclic group.
Selective serotonin reuptake inhibitors (SSRIs) do not stimulate

appetite and have much fewer antimuscarinic side effects than

the tricyclics and other catecholamine-uptake inhibitors. They

are also well tolerated in the elderly. Examples include fluox-

etine,fluvoxamine,paroxetine,sertraline,citalopramand

escitalopram.

Uses

These include the following:

1. in depression (they have similar efficacy to tricyclics, but
   are much more expensive);
   2.in chronic anxiety, and as prophylaxis for panic attacks;
   3.obsessive-compulsive states;
   4.bulimia nervosa;
   5.seasonal affective disorder, especially if accompanied by
   carbohydrate craving and weight gain;
   6.possibly effective as prophylactic agents in recurrent
   depression.

Adverse effects

1. The most common adverse reactions to SSRIs are nausea,
   dyspepsia, diarrhoea, dry mouth, headache, insomnia and
   dizziness. Sweating, erectile dysfunction and delayed
   orgasm are well-recognized associations. These tend to
   become less severe after one to two months of treatment.
   2.They have less anticholinergic and cardiotoxic actions
   than tricyclic drugs.

Table 20.1:Relative antidepressant side effects

Drug Anticholinergic Cardiac Nausea Sedation Overdose Pro-convulsant Tyramine

effects effects risk interaction

Tricyclics and related

antidepressants

Amitriptyline       

Clomipramine       

Dothiepin       

Imipramine       

Lofepramine     

Trazodone       

Selective serotonin

reuptake inhibitors

Citalopram 

Fluoxetine ? 

Paroxetine ? 

Sertraline ? 

Monoamine oxidase

inhibitors

Phenelzine       

Moclobemide   ? 

Others

Venlafaxine ? 

, little or nothing reported; , mild; , moderate; , high; ?, insufficient information available.