PsychoTropicalResearch, serotonin and serotonin syndrome research.
Antidepressants - Which one; basics for dummies
Antidepressants - Which one; basics for dummies
Date Created: 07/07/2001 Last Modified: 06/04/2002 Last Checked: 23/01/2003
Depressive illness responsive to drugs cannot be reliably distinguished from other depressive states except by its response to anti-depressant drugs. There are no tests or diagnostic criteria or rating instruments able to make this distinction. No blood tests (eg like the DST dexamethasone suppression test) are of clinical utility. A trial of a drug is a good way of discovering what the effective or optimum type of treatment will be. A trial of a less effective drug is thus especially confusing and unhelpful.
A significant number of supposed anti-depressant drugs that have been approved for marketing (over the last 30 yrs) subsequently failed to prove themselves to possess antidepressant efficacy in general clinical use. Others are still used a bit but regarded as weak antidepressants by many experienced psychopharmacologists. Recent examples are moclobemide and nefazodone. Doctors who follow a logical treatment and prescribing sequence will rarely use them because they will have referred to specialists before they get that far (it is usually logical to refer if two treatment attempts have failed to induce full remission- see 'When to refer').
For major ('endogenous') depressive illness selective serotonin reuptake inhibitors are less effective than amitriptyline. The indications are that the more severe the illness the less well SSRIs, and many other newer drugs, work. Clinical experience supports that even more strongly than does meta-analysis.
Remember response rates quoted for drugs trials may seem good, but they relate to a 50% decrease in rating scale scores, which is a much less stringent criterion for success than wellness or full remission.
Sertraline is a logical first choice, especially in less severe cases and where first line treatment with a tricyclic antidepressant is not appropriate (eg see note 538). Most selective serotonin reuptake inhibitors have problematic cytochrome P450 interactions; these are fluoxetine (2D6 and 3A4), paroxetine (2D6) and fluvoxamine (1A2 and 2C9 /19), so I consider it is hard to logically justify their routine first line use in primary care.
If side effects have resulted in an inadequate therapeutic trial then a second serotonin reuptake inhibitor may be tried. The next choice may be venlafaxine or citalopram.
I prefer usually to switch classes and use a tricyclic antidepressant (TCA). Nortriptyline has a good side effect profile and near-linear pharmacokinetics (also blood levels are easily done). Since interactions between sertraline or citalopram and nortriptyline are straightforward to allow for and manage I usually allow an overlap and start the nortriptyline before attempting to cease the serotonin reuptake inhibitor. This strategy often produces such a good result that patients do not wish to cease the serotonin reuptake inhibitor; if either of the two drugs is ceased a worsening of depression severity is frequent. Hence continuation of this "SNRI" approach is the rule.
All text ©Dr Ken Gillman MRC Psych - PsychoTropical Research®
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