Date Created: 16/01/1999 Last Modified: 16/01/2002 Last Checked: 07/01/2003

Now that the SSRIs have been in use long enough to be seen in perspective it is clear they have side effect differences from the TCAs, with some advantages, albeit modest. These advantages may not be as great some wish them, or perceive them, to be.

The overall discontinuation rate of SSRIs is 25%. Discontinuation rates of TCAs are very similar. These figures comes from controlled trials and may not be representative of the clinical situation or of longer term use.

Some serious side effects, eg GI problems, hyponatremia, seem to be higher with SSRIs than with TCAs.

Some SSRIs interact with other drugs (via cytochrome P450 enzymes) more frequently than do the TCAs. With paroxetine, fluoxetine and fluvoxamine this is such a potentially serious problem that doctors who do not have an adequate knowledge of cytochrome P450 enzyme interactions would be well advised to avoid these drugs where any possibility of an interaction is present.

There may be significant differences between the different SSRIs, both in side effects, efficacy and possibly toxicity. The nature of these differences may be partly understood by remembering that the TCAs are defined as a ‘class’ by virtue of their structural (tricyclic) similarity - some of their pharmacological actions are quite diverse. In contrast the ‘SSRIs’ are defined as a class by their action, not by their structure, which is quite different for each one.

It seems that patients who fail to respond to one SSRI may respond to a different SSRI -- trying more than two SSRIs is probably not the best course; at this stage reassessment / a trial of a different class of drug / referral are likely to be indicated.