Antidepressants can be considered for people with moderate to severe depression, and may also be prescribed for milder cases that have not benefited from psychological therapy. Treatment should be continued for at least 6 months after remission.
Monoamine oxidase inhibitors (MAOIs) irreversibly inhibit both MAO-A and MAO-B. They are advocated for atypical depressives with anxiety and somatic complaints, patients resistant to TCAD therapy, and those with agoraphobia. The dangers of dietary and drug interactions should be considered, see MAOIs entry in section. The reversible selective MAO-A inhibitor moclobemide is thought to have fewer systemic effects and a reduced risk of interactions. Reversibility is also thought to reduce the length of the wash-out period required when transferring to other antidepressants.
Selective noradrenaline reuptake inhibitors are highly selective and so have fewer side effects than TCADs. They are particularly useful for alleviating the negative symptoms of depression. Similarly, selective serotonin and noradrenaline reuptake inhibitors (SNRIs) do not have the side effects associated with the TCADs.
Selective serotonin reuptake inhibitors (SSRIs) are better tolerated, less sedative and less cardiotoxic, have fewer antimuscarinic side effects and are safer in overdose than TCADs. Side effects include nausea, diarrhoea, headache, insomnia, agitation and sexual dysfunction.
The tricyclic antidepressants (TCADs) with sedative properties (amitriptyline, dosulepin, doxepin and trimipramine) may be of greater benefit in depression with high levels of anxiety and agitation. Those with weak sedative or stimulating properties (clomipramine, lofepramine, nortriptyline) may be more useful in lethargy. All have significant antimuscarinic effects and should be used with extreme caution in glaucoma, urinary retention, pyloric stenosis and prostatic hypertrophy. Tolerance to these effects may develop and may be reduced if low doses are given initially and then gradually increased. When the patient responds, he/she initially sleeps better and stops losing weight. A quickening in thought, speech and activity usually follows and finally mood lifts. Anxiety, however, may persist. Some patients with depression do not recover completely but continue with a chronic syndrome controlled by the TCAD. Other indications for TCADs include obsessive-compulsive disorder and phobic states.
The tricyclic-like antidepressant trazodone has fewer antimuscarinic side effects than TCADs and is safer in overdose. Its sedative properties are useful against concomitant anxiety.
Mianserin, a tetracyclic antidepressant, has much reduced cardiovascular and antimuscarinic side effects compared with the TCADs.
Other antidepressants include agomelatine, which has been shown to have a beneficial effect on disturbed sleep patterns and a neutral effect on body weight, heart rate, blood pressure and sexual function. Esketamine is the S-enantiomer of ketamine and can be effective in patients with treatment-resistant depression; it is given in combination with a SSRI or SNRI. The antispychotic flupentixol, given in low doses, can improve symptoms of apathy, lowered mood, asthenia, despondency, lack of initiative or inertia. The a2 antagonist mirtazapine increases noradrenergic and serotonergic neurotransmission. Quetiapine can be given as an add-on treatment in patients who have a suboptimal response to antidepressant monotherapy. Vortioxetine has a multimodal action including SSRI activity and modulation of activity at several serotonin (5HT) receptors. It may improve cognitive symptoms of depression.
Lithium salts are used in recurrent depression, as well as in mania and bipolar disorder. The carbonate salt is more widely used but the citrate is also available. Lithium salts have a narrow therapeutic/toxic ratio and treatment requires facilities for monitoring serum levels. Bioavailability varies from product to product, particularly sustained-release preparations, therefore, lithium preparations should be prescribed by brand name and patients should not be transferred from one preparation to another without full clinical assessment and retitration.
Note Hyponatraemia may be associated with all types of antidepressants and should be considered in any patient who develops drowsiness, confusion or convulsions.
All patients should be monitored for suicide-related behaviours at the start of treatment until significant improvement in condition is seen. Patients with a history of suicide-related events and young patients should be monitored throughout treatment. Suicide-related behaviours and hostility were more frequently observed in children. In addition, long-term safety data in children concerning growth, maturation and cognitive and behavioural development are lacking. Patients and carers should be advised to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.