2.13 Treatment guidelines and prescribing modes
Shortly after the launch of the Defeat Depression Campaign, a Consensus Statement was published on recognition and management of depression in general practice. One of the prime movers (Priest) was also the Chairman of the Campaign. The consensus statement and the Campaign were closely linked, though the authors of the statement emphasised that their guidelines "do not necessarily reflect the official policy of either of the two colleges" (Paykel & Priest, 1992). The statement emerged from the proceedings of two conferences, each involving about 20 participants; no indication was given of any sources of support.
The statement began by referring to the tendency to prescribe tricyclics at ineffective doses, noting also that "many newer compounds are less toxic in overdose and have fewer side effects." However, the major change was the recommendation to extend the duration of treatment. Previously, the general idea had been to treat patients with antidepressants for several weeks and then reduce the dose by about half and/or discontinue the drug. This was the advice given in the British National Formulary until March 1996:
"Treatment should be continued for 2 weeks before suppression of symptoms can be expected and thereafter should be maintained at the optimum level for at least another month before any attempt is made at dose reduction ..."
By contrast, the recommendation in the Consensus Statement was to continue treatment at the original dose, at least for a few months:
"... four to six months of antidepressant therapy after the initial treatment phase is advocated to prevent relapse. There is no reason for a steep reduction to a maintenance dose, and drugs should be continued close to the dose at which a clinical response was achieved, unless side effects make this unacceptable ..."
Over the years, increasing emphasis has been placed on the need for long-term or lifetime treatment, to prevent relapse. One turning point can be traced to the end of the 1980s, when the Committee on Safety of Medicines finally issued new guidelines for prescribing benzodiazepines, to limit the risk of dependence. (CSM, 1988) The new guidelines restricted BDZ prescribing to a maximum of a few weeks; before then they could be prescribed indefinitely and often were. At the same time, the British National Formulary deleted its long-standing recommendation to consider prescribing BDZs and antidepressants together, immediately replacing it with a statement suggesting the benefits of long-term use of antidepressants on their own:
"It may be appropriate during the early states of treatment to add a hypnotic to correct the sleeping pattern or an anxiolytic to allay anxiety or agitation." (BNF, No 18, September 1989)
"In recurrent depression, prophylactic maintenance therapy may need to be continued for several years." (BNF, No. 19, March 1990)
The Consensus Statement developed this theme. Depression did tend to be recurrent and was potentially dangerous too, and the evidence showed that antidepressants reduced the incidence of relapse. Patients more likely to relapse than others, who would be candidates for long-term therapy, not only included those with a history of previous episodes of depression but also "patients who lack social support, and patients with continuing social difficulties (such as unemployment or dysharmony in interpersonal relationships)". In addition:
"The patient clearly should be given as much information as possible in deciding whether to continue. Advice should include the facts that antidepressants are not habit-forming or addictive and that a minimum of four months treatment is advised for classic depression to prevent relapse. This will enable the patient better to make an informed choice about continuation with treatment." (Paykel & Priest, 1992)
In spite of this emphasis on involving patients, the guidelines were clearly designed by professionals for professional use. They addressed the abiding public concern (Priest et al., 1996) that antidepressants were drugs of dependence simply by denying it. The guidelines may or may not have been designed partly with fear of litigation in mind, but they hint of "defensive medicine" and would certainly have reduced any risk. The chances of a successful action would be small, when depression was clearly identified as a potentially dangerous condition, yet under-recognised and undertreated; if the need for and benefits of long-term antidepressant use were widely advocated; also if the most authoritative definition of "dependence" pointed irresistibly to problems with the user, rather than to shortcomings of the drugs. See 3.5
The Consensus Statement went on to suggest that, even in less serious cases, drugs could prevent depression "for up to three years". This (and other) recommendations represented a significant departure from the claims a manufacturer would be allowed to make in the official prescribing reference document, the Data Sheet (UK) or Label (US). For example, the US Label for Prozac says this:
"The efficacy of Prozac "was established in 5- and 6- week trials with depressed outpatients ... the antidepressant action of Prozac in hospitalised depressed patients has not been adequately studied ... The effectiveness of Prozac in long-term use, that is, for more than 5 to six weeks, has not been systematically evaluated in controlled trials ..." (Lilly, 1996)
As well as advocating longer-term use, the Consensus Statement emphasised that doctors should be prescribing at higher dosages than most used. A major analysis of GP antidepressant prescribing (involving examination of 80,000 NHS prescriptions written in early 1993) indicated a gulf between recommended practice and normal prescribing regimes. It was found that 9 out of 10 prescriptions for tricyclics were for dosages below those recommended in the Consensus Statement and that 4 out of 10 were for less than 6 months (Donoghue & Tylee, 1996). A similar picture emerged in the US: the Consensus Statement on the Undertreatment of Depression reported that "the vast majority of those treated with antidepressant medication are not prescribed an adequate dose for a long enough time"; taking into account the extent of underdiagnosis, "only about one in ten of those suffering from depression received adequate treatment" (National Depressive and Manic Depressive Association, 1997).
However, the perceived problem of low dose prescribing mainly concerned the tricyclics, the evidence suggesting that "newer antidepressants (lofepramine and the SSRIs) are prescribed comparatively well". This finding has been interpreted as another reason for recommending general practitioners to use SSRIs. (Donoghue & Tylee, 1996) It also raises an issue directly relevant to the question "Do antidepressants work?" If SSRIs are prescribed at therapeutic doses, but tricyclics are used at doses which have effects on depression comparable to placebos, why has there been no corresponding evidence of the superiority of SSRIs ?
Whatever the answer, "prescription of correct dosages and deciding upon appropriate maintenance therapy are difficult areas in antidepressant prescribing for both general practitioners and psychiatrists". (Kerr, 1994) For GPs in particular the problems start with the diagnosis. The originator of the Hamilton Scale for Depression suggested that "an adequate interview will surely not be less than half an hour" (Hamilton, 1967) much longer than the average GP would be able to spend. The situation may be comparable in the US: a 1993 study by the Rand Corporation reportedly found that over half the physicians surveyed wrote prescriptions after discussing depression with patients for three minutes or less. (Wurtzel, 1996)
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