Choice of drug

Patients in whom depression is accompanied by agitation or insomnia are most likely to benefit from one of the more sedative tricyclics such as amitriptyline, dothiepin, or trimipramine, whereas patients with psychomotor retardation may be better on a non-sedating drug such as imipramine, lofepramine, or nortriptyline.

The side-effect profile may determine the choice of drug, especially in patients with co-existing medical disorders. Compounds such as amitriptyline tend to produce more unwanted effects than the newer ones, yet, for some patients, they appear to be more effective as antidepressants.

If depression proves resistant to tricyclics, another drug may be added. Lithium augmentation is sometimes helpful. Combined therapy of a tricyclic with an SSRI or MAOI (see below) is another option but may be hazardous, so it should be used only by experienced specialists.

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