PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. Antidepressants - Combinations.

PsychoTropicalResearch, serotonin and serotonin syndrome research.

Antidepressants - Combinations

Antidepressants - Combinations

Date Created: 14/01/1999   Last Modified: 07/10/2002   Last Checked: 17/04/2002

Combinations of SSRIs and TCAs are either implicitly or explicitly proscribed by specialist colleges in both Australia and the UK.

The general view, at present, seems to be that there is insufficient evidence such combinations are more effective. Not all experience accords with that, selected combinations may be efficacious.

There are some risks and pitfalls if you do not have an extensive understanding of psychopharmacology.

In view of the prevailing opinion about this, and the toxicity of some TCAs, it may be wise to avoid initiating such regimes in general practice. Remember, It is quite possible to enter the area of significant mortality risk if you combine different types of antidepressant, eg especially SSRIs and TCAs and SSRIs and neuroleptics.

Monitoring of TCA plasma levels is usually prudent.

Many clinicians do find such combinations of great value. I frequently use sertraline and nortriptyline which is a particularly satisfactory combination. It may well be that such ‘dual therapy’ that boosts both serotonin and noradrenalin will become more widely accepted before long.

Combinations of MAOIs and TCAs may occasionally be used in specialist practice; but not all specialists have sufficient knowledge or experience to do this safely; it is doubtful that there is much to be gained from the technique except in special circumstances. The main danger is serotonin syndrome which can be fatal. This is likely to be caused by:-- MAOIs (including RIMAs such as moclobemide) when they are combined with 'SSRIs', or any TCA which is also a serotonin reuptake inhibitor (SRI) especially clomipramine and imipramine, or venlafaxine, sibutramine or milnacipran.

TCAs that are essentially only noradrenalin reuptake inhibitors (which is in fact most of them-- see receptor affinities) are quite safe when combined with MAOIs. So adding a small dose of amitriptyline, nortriptyline or doxepin to improve sleep (via H1 blockade, and perhaps 5-HT2A blockade) in a patient on MAOIs is most unlikely to cause any major side effect problems and does not give rise to a significant risk of serotonin syndrome.