The problems of safety and compliance with conventional antidepressant drugs.

The incidence of unwanted effects with tricyclic antidepressants usually ranges between 15% and 30%. Adverse effects particularly involve the autonomic nervous system and the cardiovascular system, and sedation is common. Tricyclics interact with many other drugs including antihypertensive agents, monoamine oxidase inhibitors (MAOIs), anticholinergic drugs, antihistamines and sedatives (especially alcohol). Overdoses of tricyclics are hazardous, producing respiratory and cardiac depression, fits and coma. Compliance is poor with tricyclic antidepressants, mainly due to the side-effects, particularly sedation and dry mouth, and to a failure in doctor-patient communication. The range of pharmacological effects, wanted and unwanted, reflects the relative lack of selectivity of these drugs: more selective drugs should be advantageous in the treatment of depression.