Considering the Drug & Therapeutics Bulletin is published by Consumers Association, this review seems fairly complacent about the risks of drug treatment for depression. True, there is something in this review to please just about everyone - or at least console them - but that is why it misses the mark. By trying not to offend anyone too much, the DTB in effect denies the controversy and problems that surely exist. The way in which the review fudges the question, "dependence or not?" illustrates this:
"From the patient's point of view discontinuation symptoms would be highly important if they resulted in any marked degree of difficulty in stopping the treatment, and might well feel tantamount to dependence."
This is one of several "exclusion clauses" in the review, obfuscation in small print that steers from the point. If the same information had been imparted clearly enough and in plain English, patients might have understood much more. What the DTB seems to be saying (but did not) is that no-one should be surprised if perhaps one in ten people who start taking antidepressants later find they have become (in their terms) addicted to these drugs.
The main obstacle to candour is that the term "dependence" was radically redefined by the American Psychiatric Association (APA, 1994). The DTB notes this, but questions neither its causes nor implications: why does it make sense to change a definition, making it much harder to define anything as "dependence" which does not resemble frank abuse? The reviewers just blandly state that "there is a general perception that withdrawal is indicative of dependence", but then undermine the point by affirming that "as currently defined, dependence requires the presence of other features such as a compulsive desire to take the drug, difficulty controlling level of use despite evidence of harm, neglect of other pleasures, and evidence of tolerance". One need only refer back to the DTB's advice on benzodiazepines (published 25 years after they first came to market) to sense the trouble now in store:
"The extent of pharmacological dependence on benzodiazepines was not fully appreciated until recently. This was probably because prominent features of drug dependence, such as tolerance and consequent escalation of dosage, are uncommon among patients starting on normal doses. The chief manifestation is a withdrawal syndrome on stopping the drug" [DTB, 1985].
This new DTB review uses a definition of "withdrawal syndrome" proposed by Malcolm Lader in 1983. However, it does not come to the central point Lader sought to make a decade later - that withdrawal symptoms on their own clearly indicate some physical dependence:
"My own studies (with Hallström and Pétursson) established unequivocally that normal dose dependence as manifested by a physical withdrawal syndrome was a definite entity and supervened even if the dosage was tapered off. Tolerance with escalation of dosage was not a prerequisite for physical dependence. Indeed our initial study compared withdrawal syndromes in small groups of patients withdrawing from high dose misuse or low dose use and found that the syndromes were identical"
Essentially the same point was underlined (1990) by the APA's Task Force report on Benzodiazepine Dependency: "The presence of a predictable abstinence syndrome following abrupt discontinuance of benzodiazepines is evidence of the development of physiological dependence " It seems almost self-evident that the public, the media, and also many doctors, would have been badly misled by the redefinition that has gone on since.
The DTB adds symbolically to the confusion by electing to use the US approved redefinition of withdrawal symptoms as a "discontinuation syndrome" - though when the CSM was last year formally invited to adopt this term, they wisely decided "that it would be inappropriate to change medical terminology in this way". The DTB's justification is that the term is "commonly" used - but surely most members of Consumers Association would never use it at all.
There are two underlying reasons for all the confusion. One is a sort of well-meant but misguided belief that depressed patients should not be burdened by bad news. The other is that, once you acknowledge the reality of dependence, you open a can of worms. It brings you right back to the question of whether "relapse" of depression actually exists to anything like the extent claimed.
In another exclusion clause, DTB acknowledges that "ignorance of discontinuation reactions could have led, in the past, to some overestimation of relapse rates". But then it cites as "strong evidence" for the existence of relapse, three papers (none a randomised controlled trial) all written before the antidepressant withdrawal problem was recognised as it is now. The real worry, not addressed in this review, is that much of the recurrent depression believed to exist today might result from 'sensitisation' to drug effects - ie the use of antidepressants might make patients more vulnerable to subsequent episodes of depression (Keller, 1994). Nor does this DTB review refer to much of the other evidence that suggests that risks for patients may be greater than generally supposed. For example:
In short, it is going to take more time for the medical establishment to come to its senses. In the meantime, this review does some disservice to consumers, even if it adds to the evidence that the difference between "relapse" and "withdrawal" is extremely confused.
Declaration of interest The author declined invitations to review two earlier drafts of this DTB review, believing this might have compromised his ability to offer criticism of it after publication. The original draft omitted any reference to The Antidepressant Web, but the DTB later said they would carefully consider it - another factor in the decision not to comment. Medawar has had a long and generally very happy association with both Consumers Association and the Drug & Therapeutics Bulletin (and would wish it to continue).