The best treatment of anxiety may not involve the drugs that recent literature suggests
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A recent data analysis that was published in the British Medical Journal (BMJ) suggested that antidepressant drugs may offer the best treatment for generalized anxiety disorder. This new data analysis that is published in the recent issue of Psychotherapy and Psychosomatics suggests that BMJ is faulty and biased by conflict of interest.
Generalized anxiety disorder, the constant and fearful worry and fearful anticipation of events, is a common disturbance. A recent data analysis that was published in the British Medical Journal (BMJ) suggested that antidepressant drugs may offer the best treatment for generalized anxiety disorder. A new data analysis that is published in the recent issue of Psychotherapy and Psychosomatics suggests that BMJ is faulty and biased by conflict of interest.
In Baldwin and colleagues’ paper, trials were selected if they could allow determination of ‘response’ (the proportion of patients who experienced a reduction of at least 50% of their baseline score on the Hamilton anxiety scale) and ‘remission’ (the proportion of patients below a certain cutoff point on the scale). The authors failed to justify the choice of outcome measures, which have two major disadvantages: in generalized anxiety disorder we are dealing with a decrease in symptom intensity more than with a simple presence or absence, and categorization is hindered by the availability of different versions and translations of the Hamilton scale. Indeed, unlike what is commonly found in individual trials, response and remission did not correlate well in the meta-analysis, probably since this categorization is likely to be affected by the different characteristics of the trials, maximizing the inherent tendency of meta-analyses to violate the internal validity of the placebo comparison.
Another very questionable procedure was to infer tolerability from withdrawals that may have been due to a number of reasons. This choice of outcome measures excluded a great number of studies concerned with older and low-cost medications, such as benzodiazepines, despite a large body of evidence pointing to their efficacy in generalized anxiety disorder. Only two trials included a benzodiazepine (lorazepam), and no trial used a tricyclic. By using categorical inclusion criteria, Baldwin and colleagues obtained 26 studies that were published in 2001 or later and one that was published in 1999. It is unclear how many studies were eligible for inclusion but for the absence of the specific outcome measures chosen. Some clinical points required for a critical appraisal of data from meta-analyses and systematic reviews were missing from the discussion. First of all, mention should be made of the fact that drug treatment is not mandatory in generalized anxiety disorder, and psychotherapies, in particular cognitive-behavior therapy, are at least as effective as pharmacological treatments. Second, Baldwin and colleagues acknowledged the fact that they could only evaluate the initial phase of treatment (6–8 weeks), whereas generalized anxiety disorder is a chronic condition that requires long-term treatment. There is emerging awareness of serious and bothersome side effects that may ensue with long-term treatment with selective serotonin reuptake inhibitors (SSRI), such as high rates of sexual dysfunction, bleeding (in particular gastrointestinal), weight gain, risk of fracture and osteoporosis, and hyponatremia. Further, generalized anxiety disorder frequently occurs in the setting of medical disease. An issue that is frequently underestimated is the potential for drug interactions of antidepressant drugs, with special reference to the SSRI medications. Both in terms of long-term treatment side effects and potential for drug interactions, benzodiazepines appear to be much safer than antidepressant drugs. It may well be that the only potential advantage of SSRI versus benzodiazepines is represented by a lower impairment in cognitive and psychomotor skills. Finally, there are two additional areas of concern regarding long-term treatment with antidepressant drugs in anxiety disorders. First, loss of clinical effect, with return of symptoms that is often refractory to drug increase, has been reported. Second, there is also the risk that antidepressant drugs in anxiety disorders may actually predispose users to major depressive episodes.
The disclosure requirements of the British Medical Journal allow the reader to reconstruct the genesis of the paper by Baldwin and colleagues, and may shed some light on methodological choices and critical omissions present, including the fact that the authors neither specifically searched for unpublished studies nor additional data. Although the study was allegedly independent, all authors had financial ties with Lundbeck and other pharmaceutical companies which manufactured the drugs that were included and discussed in the meta-analysis. The meta-analysis performed by Baldwin and colleagues is likely to yield misleading conclusions, particularly for the busy clinician who has no time to check its faulty procedures and the lack of appropriate clinical integration. The publication of this paper calls for a reassessment of journals’ policies concerned with reviews, editorials and meta-analyses.
Source:Journal of Psychotherapy and Psychosomatics Fava, G.A. Statistical Alchemy for Drug Treatment of Generalized Anxiety Disorder: A Commentary on the Meta-Analysis by Baldwin et al. [BMJ 2011;342:d1199]. Psychother Psychosom 2011;80:261-263
