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Antidepressants - Choices, which type first?

Date Created: 20/06/1999   Last Modified: 07/10/2002   Last Checked: 03/01/2003

Can we predict which patients will do better on tricyclic antidepressants rather than serotonin reuptake inhibitors, as a first choice treatment?

Yes, a substantial proportion of patients will benefit from having a TCA as their first choice, especially if they have a typical "endogenous", or more severe, depressive illness.

Reasons for choosing a TCA before an SSRI.

1. Patients with previous episodes of severe depression (especially if it was unresponsive, or only partially responsive, to an SSRI).
2. Those whose current episode is severe or shows psychomotor retardation or lack of energy (optimal choices, amitriptyline and clomipramine, my preference is definitely for clomipramine because it is an 'SNRI").
3. Those with pre-existing history of, or present symptoms of, marked insomnia.
4. Those with pre-existing symptoms / history or present symptoms of gastrointestinal disturbance, GI bleed, reflux, dyspepsia.
5. Those with present or past history of significant suicidal features. Such patients may be made worse by SSRIs and there is some concern that in a small number a feeling of restlessness (induced by SSRIs) may increase suicidal risk. There is no risk of over-dose with the prescribed TCA, because, as part 'good clinical management', patients will be attending frequently. A small supply may be issued at each visit if no responsible person is available to supervise the supply. Remember-- 95% of those who die by suicide use means other than the drug they are given by you.
6. Those with high anxiety or agitation (may be especially at risk re 5 above).
7. Those with anorexia and weight loss.
8. If concern over cytochrome P450 enzyme drug interactions is relevant. TCAs cause less problems in this area than many new drugs.
9. A history of hyponatremia.

The above factors, and various others, suggest a TCA may be the optimal first choice.

Gillman's maxim No. 2

The longer a new drug is in use the smaller its side effect advantages turn out to be, compared with previously existing drugs.

There is evidence from both clinical experience and research that SSRIs increase the risk of gastric bleeds and disturbance. This is probably for two reasons; they increase the bleeding time (by depleting platelet 5-HT) and they are 'pro-kinetic' in the GI tract (hence the side effect of diarrhoea) and that may promote worsening of GI problems.

It behoves us all to be alert and sceptical in this area. Post marketing surveillance in most countries is a relatively neglected area; we must not expect that side effects will always be obvious.

All text ©Dr Ken Gillman MRC Psych - PsychoTropical Research®


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