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The 'efficacy' of alprazolam in panic disorder and agoraphobia: a critique of recent reports
... This finding is similar to studies with other agents (SSRIs) in PD that demonstrate high relapse rates after treatment cessation ( Mavissakalian and Perel, 2002;Toni et al., 2000). A major issue with this trial was patient drop-out, most notably in the placebo arm, which has led to debate over the validity of these results (Marks et al., 1989). However, given the large number of controlled trials supporting efficacy of alprazolam in controlling symptoms of PD ( Andersch et al., 1991;Curtis et al., 1993) the WFSBP guidelines have attributed it with category A evidence ('full evidence from controlled studies') ( Bandelow et al., 2008) for PD treatment. ...
To investigate the potential impact of increasing prescription rates of alprazolam for the treatment of panic disorder (PD) in Australia through a review of efficacy, tolerability and adverse outcome literature.
Data were sourced by a literature search using MEDLINE, Embase, PsycINFO and a manual search of scientific journals to identify relevant articles. Clinical practice guidelines from the American Psychiatric Association, National Institute of Clinical Excellence, Royal Australian and New Zealand College of Psychiatrists and World Federation of Societies of Biological Psychiatry were sourced. Prescription data were sourced from Australian governmental sources.
Alprazolam has shown efficacy for control of PD symptoms, particularly in short-term controlled clinical trials, but is no longer recommended as a first-line pharmacological treatment due to concerns about the risks of developing tolerance, dependence and abuse potential. Almost no evidence is available comparing alprazolam to current first-line pharmacological treatment. Despite this, prescription rates are increasing. A number of potential issues including use in overdose and impact on car accidents are noted. conclusion: Although effective for PD symptoms in clinical trials, a number of potential issues may exist with use. Consideration of its future place in PD treatment in Australia may be warranted.
Because the epidemic dispensing of psychiatric drugs is based on misinformation, it is important for all health professionals, consumers, and most citizens (including patients and their family members) to have a more rational understanding of how psychiatric drugs actually “work.” Instead of enforcing authoritarian “medication compliance” in obedience to the prescriber’s orders, informed therapists and healthcare providers have an ethical duty to provide scientific information about the real effects of psychiatric drugs. Instead of naively accepting whatever the doctor prescribes to them, consumers need to educate themselves about all medications, but especially about psychiatric ones, which are consistently misrepresented and oversold. This review focuses on three principles of rational psychopharmacology. The first is the brain-disabling principle, which states that all psychoactive substances work by causing dysfunctions of the brain and mind. It further observes that no psychiatric drugs work by improving or correcting biochemical imbalances or any other presumed biological malfunctions. The second principle is intoxication anosognosia (medication spellbinding) which states that all psychoactive substances tend to cause a subjective over-estimation of their positive effects while masking their harmful ones, sometimes resulting in extremely harmful behaviors such as mania, violence and suicide. The third principle is chronic brain impairment (CBI)—that exposure to psychoactive substances, especially long-term, results in impairments of the brain or mind that can become persistent or permanent, including atrophy (shrinkage) of brain tissue. Not only are psychiatric drugs likely to do more harm than good, there are more effective and infinitely safer proven psychosocial approaches for treating the whole spectrum of “psychiatric disorders” from “ADHD” and “major depressive disorder” to “schizophrenia.”
Benzodiazepines are generally considered safer than previously used sedatives and hypnotics (e.g. opiates and barbiturates). In the past decade, however, they have generated considerable controversy. Although much of the ongoing debate about benzodiazepines tends to centre on issues related to their dependency and abuse potential, problems also may occur with their therapeutic use. Despite a lack of study evidence demonstrating that benzodiazepines have continuing therapeutic efficacy beyond 6 months for anxiety and 4 weeks for insomnia, an unknown number of patients have taken benzodiazepines for extended periods, in some cases for up to 25 years or more. Other than increased risk of withdrawal reactions, little is known about the effects of protracted benzodiazepine use on health and cognitive function. A number of investigators, however, have reported considerable ill health, both mental and physical, in long-term users. Short-term therapeutic use of benzodiazepines is often considered relatively risk-free. Problems, however, also may occur with brief administration of some benzodiazepines, particularly alprazolam and triazolam. Although no new class of drugs has emerged as a clear replacement of benzodiazepines, several compounds are under investigation. In the meantime, physicians must use benzodiazepines judiciously and become adept at selecting from a range of available pharmacologic and non-pharmacologic alternatives.
Anxiety symptoms are common and distressing, and range in severity from mild and adaptive to transcendentally severe and disabling.
Anxiety symptoms are caused by and comorbid with many medical and psychiatric illnesses. Anxiety diagnoses virtually always
make the illness more severe and disabling, more difficult to treat, and make the prognosis worse.
1.1. The charts of 78 panic disorder outpatients treated with alprazolam (mean dose 4.30 mg/day, mean duration 31.9 months) were reviewed for demographics, past history (including substance abuse and major depression), and evidence of alprazolam abuse. In addition, the patients were evaluated by Clinical Global Index for improvement at last contact.2.2. Moderate to significant recovery was found in 77% of patients. Major depression was seen in 41%. Depressed patients were more likely to have coexisting agoraphobia and a past history of alcohol abuse than non-depressives.3.3. There was no DSM-III-R anxiolytic abuse, but 12% showed unauthorized use of the alprazolam. These subjects were three times more likely to have a history of drug abusethan non-misusers.4.4. These results indicate that alprazolam is effective in the long-term treatment of panic disorder, but that prolonged management may be required. Further, the data raise concerns about use in panic patients with substance abuse histories.
Cultural and economic influences on the psychopharmacological era are reviewed, in an attempt to bring into focus what has been happening in psychopharmacology for the past thirty years. It is argued that the belief that clinical advances are made through the heroic achievements of disinterested scientists is a simplistic view that may militate against future significant discoveries. Such discoveries, it is argued, still come about for the most part serendipitously, despite a widespread belief that psychopharmacology has become a rational science.
Among 79 volunteer, unpaid, family doctor-referred psychiatric out patients with DSM III-R panic disorder, with and without agoraphobia, 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months. All subjects received one hour per week concurrent behavioural counselling in the acute phase. Of 13 dropouts in the first 3 weeks, 9 (of 27) were on clomipramine, 2 (of 26) were on lofepramine and 2 (of 26) were on placebo. The high (30%) early dropout from the clomipramine group was largely due to medication intolerance. Both drugs were superior to placebo by the end of week 6 on several standard rating scales but not on panic attack frequency. No significant differences in efficacy were found between the two drugs tested to the end of 6 months. No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24. The study provides evidence that both drugs, in the dosages used, are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy.
Drug treatment of panic disorder is reviewed with focus on recent controlled studies. The efficacy of alprazolam, a triazolobenzodiazepine, and imipramine, a tricyclic antidepressant, has consistently been demonstrated, but there is reasonable evidence that other benzodiazepines or antidepressants might also be effective if equipotent doses are used. Most controlled studies demonstrate drug efficacy on several psychopathological symptoms, including the core symptom panic attacks. Limited evidence indicates that alprazolam may be more efficacious in treating panic attacks than avoidance behaviour, and the reverse when imipramine is concerned. Drug efficacy appears to be most consistently documented in moderately to severely ill panic patients. The benzodiazepines are better tolerated than antidepressants in terms of patient acceptance, and the improvement sets in faster with benzodiazepines. In the presence of depressive symptoms considered secondary to panic attacks and/or agoraphobia, both types of drugs appear efficacious. Difficulty discontinuing high-dose benzodiazepine treatment remains the most important side effect of the treatment but sedation can, like anticholinergic side effects of the tricyclic antidepressants, be troublesome, thereby diminishing patient compliance. The role of newly developed antidepressants with a more specific mode of action and milder side effects awaits evaluation in controlled trials.
Before 1980, most people experiencing common nervous problems and who sought medical help complained of anxiety and were treated for anxiety. Similar experiences increasingly led to complaints of or treatment for panic attacks in the late 1980s and early 1990s, and to complaints of or treatment for mood disorders by the mid-1990s. Today, such patients seem once again increasingly likely to complain of and be treated for anxiety. This paper reviews a series of mechanisms whereby company marketing can both transform the perceptions of physicians and shape the experiences of those seeking treatment and the self-understanding of those not in treatment. These include the standard ploys of company sales departments to increase demand for products, including celebrity endorsements, the sponsoring of educational events and a host of reminders. The portfolio of marketing manoeuvres has grown, though, by translating educational events and celebrity events into the arena of scientific research: clinical trials have increasing become part of the marketing of disorders and their treatments; ghost-written scientific papers are authored by celebrity researchers. The portfolio of marketing manoeuvres has also grown to encompass new ways of creating fashion through medical activism, by setting up patient groups and disease awareness campaigns. The result is a transformation and growth in disorders tailor-made to fit ever more visible drugs.
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