General practitioners' perceptions of the tolerability of antidepressant drugs: a comparison of selective serotonin reuptake inhibitors and tricyclic antidepressants

OBJECTIVE: To examine inceptions and discontinuations of antidepressants in general practice. DESIGN: An observational study analysing data from an ongoing cross sectional postal survey. Every three months a representative sample of 250 doctors recorded prescribing activity for four weeks. This provided 4000 general practitioner weeks of recording per year. SETTING: A representative panel of general practitioners in England, Wales, and Scotland. SUBJECTS: Patients who began a new course of an antidepressant or had their treatment stopped or changed by the general practitioner between 1 July 1990 and 30 June 1995. MAIN OUTCOME MEASURES: Numbers of patients prescribed a new course of antidepressant; numbers discontinuing treatment; the ratio of antidepressant discontinuations to antidepressant inceptions; reasons for discontinuation; proportion of switches to another antidepressant. RESULTS: There were 13,619 inceptions and 3934 discontinuations of selective serotonin reuptake inhibitors and tricyclic antidepressants during the study. The number of newly prescribed courses of antidepressants increased by 116%, mostly due to an increase in prescribing of serotonin reuptake inhibitors. The ratio of total discontinuations to inceptions was significantly lower for serotonin reuptake inhibitors (22%) than for tricyclic antidepressants (33%). Differences persisted when controlled for age and sex of patients and severity of depression. However, there was more switching away from selective serotonin reuptake inhibitors when they failed (72%) than from tricyclic antidepressants (58%). CONCLUSIONS: Selective serotonin reuptake inhibitors are less likely than tricyclic antidepressants to be discontinued. A prospective study is needed in general practice to assess the implications of differences in discontinuation rates and switches on clinical and economic outcomes.     

Moclobemide. An update of its pharmacological properties and therapeutic use

Unlike older monoamine oxidase inhibitors, which irreversibly and nonselectively bind monoamine oxidase (MAO), moclobemide is a reversible and selective inhibitor of the MAO-A isozyme. Moclobemide only weakly potentiates the pressor response induced by tyramine or other indirectly acting sympathomimetics; therefore, there is no need to avoid dietary tyramine or over-the-counter decongestants with moclobemide as there is with older MAO inhibitors. Recent clinical trials and meta-analyses have confirmed the efficacy of moclobemide in the treatment of depressive disorders. Moclobemide has been shown to have similar efficacy to tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and nonselective, irreversible MAO inhibitors. Long term follow-up studies of 6 to 12 months' duration have demonstrated that the antidepressant efficacy of moclobemide is maintained. Moclobemide, given alone or in combination with another antidepressant, has shown some efficacy in patients with refractory depression; however, comparative trials are required to confirm these findings. Data are also available to show clinical efficacy of moclobemide in the management of social phobia. Comparative studies have established that moclobemide is better tolerated at therapeutic dosages and has less toxicity in overdose than TCAs and nonselective, irreversible MAO inhibitors. Moclobemide lacks the anticholinergic, sedative and cardiovascular effects associated with many of the older antidepressants. Compared with SSRIs, moclobemide has a similar overall tolerability, although it tends to cause fewer gastrointestinal effects than the SSRIs and has not been reported to interfere with sexual function. In summary, recent data which confirm and extend its comparative therapeutic efficacy and low potential for adverse effects have established moclobemide as an effective treatment in depressive disorders. The drug is also effective in patients with a primary diagnosis of social phobia. Its lack of adverse anticholinergic, cardiovascular, cognitive and psychomotor effects makes moclobemide a particularly useful option in the elderly or patients with cardiac disease.     

The cost of antidepressant overdose

Ninety percent of suicide attempts referred to a general hospital are by self-poisoning. Among women, drug overdose is the commonest means of suicide. In a retrospective naturalistic review of 200 patients who were treated in the Critical Care Unit of a general hospital following medication overdose, 12% were antidepressant overdoses. The mean duration of hospital stay for overdose with tricyclic antidepressants (TCA) was more than double that for overdose with selective serotonin reuptake inhibitors (SSRI) (7 vs 3 days; z = 2.20, p < 0.05). The dollar cost of hospital treatment for patients who overdosed on TCAs was four times greater than that for patients who overdosed on SSRIs ($22,923 vs $5,379; z = 2.30, p < 0.05). The tricyclic compounds clearly have a price advantage over more recently introduced antidepressant agents fluoxetine, sertraline, paroxetine, venlafaxine, and bupropion. The apparent cost advantage of prescribing a less expensive drug may be nullified by the cost associated with adverse consequences.     

Antidepressants as first-line agents in the current pharmacotherapy of anxiety disorders.

Over the last decade, there has been a shift in the order of medications considered as first-line treatments for anxiety disorders. This transition was largely initiated by the introduction and consolidation of the selective serotonin reuptake inhibitors (SSRIs)—fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram—in the treatment of depression, and by the subsequent extension of these agents beyond depression to various anxiety disorders, such as obsessive-compulsive disorder and panic disorder. This article reviews important clinical considerations for prescribing SSRIs for the treatment of panic disorder, obsessive-compulsive disorder, social phobia, posttraumatic stress disorder, and generalized anxiety disorder. The SSRIs and newer atypical antidepressants have established equal or superior efficacy and a more favorable side effect profile when compared to their predecessors. However, the newer agents are not without side effects, such as nausea, diarrhea, insomnia, headaches, sexual dysfunction, sedation, and weight gain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis

BACKGROUND: To determine the efficacy, safety and tolerability of antidepressants in depressed elderly patients. METHODS: Search for randomized controlled double-blind studies evaluating atypical antidepressants (ATYPs), reversible inhibitors of monoamine oxidase-A, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants in moderate/severe depressed patients > or = 60 years for > or = four weeks. The random effects model (single-arm; comparative) was used to aggregate efficacy, safety and dropout. RESULTS: No difference in single-arm aggregation of outcomes for four antidepressant classes. Comparative analyses showed no statistical difference between outcomes, except SSRIs had a higher response rate than ATYPs. CONCLUSION: Elderly show no differences in antidepressant class outcomes. LIMITATIONS: Heterogeneity and lack of power. CLINICAL RELEVANCE: There is little advantage for antidepressant classes over another in the aged.     

Selective serotonin reuptake inhibitors and atypical antidepressants: A review and update for psychologists.

Psychologists are increasingly being required to care for patients who are concurrently undergoing pharmacological treatment, particularly when patients suffer from mood disorders, such as major depression. In addition, nonpsychiatric physicians are prescribing antidepressant medications with greater frequency, thereby increasing the likelihood that the physician with which the psychologist must collaborate will have a limited understanding of psychiatric illnesses. As independent mental health professionals, psychologists have a right and a responsibility to be actively engaged in all aspects of their patients' treatment, including pharmacotherapy. A prerequisite for providing this level of professional care is a solid grounding in the principles and actions of pharmacological agents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients

The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 +/- 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (chi 2, p < .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of patients, the dysfunction disappeared completely within 6 months, but 81.4% showed no improvement at all by the end of this period. Twelve of 15 patients experienced total improvement when the treatment was changed to moclobemide (450-600 mg/day), and 3 of 5 patients improved when treatment was changed to amineptine (200 mg/day).     

Efficacy and tolerability of moclobemide in comparison with placebo, tricyclic antidepressants, and selective serotonin reuptake inhibitors in elderly depressed patients: a clinical overview

OBJECTIVE: To review the efficacy and safety of moclobemide in comparison with TCAs (for our purposes, "TCAs" will represent tricyclic and tetracyclic antidepressants, including maprotilin and mianserin) and selective serotonin reuptake inhibitors (SSRIs) in elderly depressed patients. METHODS: The efficacy data reviewed were obtained from the following sources: 1) results of published studies in the elderly; 2) data on patients aged > or = 60 years extracted from all available controlled trials in adults (> or = 18 years) in which moclobemide was compared with TCAs or SSRIs; and 3) the adverse events were extracted for patients aged > or = 60 years from the safety data base of all available comparative short-term studies with moclobemide versus TCAs, SSRIs, or placebo and of long-term studies with moclobemide. RESULTS: The data show that moclobemide is an effective antidepressant in depressed patients aged > or = 60 years. The response rate to moclobemide was 50% to 55% in this population. Moclobemide was more effective than placebo and was of similar efficacy to the TCAs and the more recently introduced SSRIs. The tolerability of moclobemide was rated as "very good" or "good" in almost 90% of these patients, which was better than the tolerability of TCAs and similar to that of SSRIs. Patients without any adverse events were more frequently found in the moclobemide group than in those treated with TCAs (P < 0.01) or SSRIs (P < 0.01). Adverse events of the anticholinergic type were more frequent with TCAs than with moclobemide (P < 0.001), and nausea was found 3 times more frequently with SSRIs than with moclobemide (P < 0.01). CONCLUSIONS: Moclobemide is an effective and well-tolerated antidepressant for the treatment of elderly depressed patients.     

Specific serotonin uptake inhibitors in patients referred to a psychiatrist

During a twelve month period (1995), 261 patients were referred to a psychiatrist (the author) by their general practitioners. Forty-eight patients (18%) were being treated with antidepressive medicine when first seen. Only seven patients were being treated with the traditional tricyclic antidepressive medicine, while 39 received specific serotonin reuptake inhibitors (SSRI) and two patients received other kinds of antidepressants. The SSRIs seem to be prescribed to a wide range of patients providing an unclear clinical picture, and it is assumed that the patients' desire to try the famous and popular pills is crucial when the therapeutic decision is made. The weakening of the ontological stase of endogenous depression should also not be underestimated.     

Association of road-traffic accidents with benzodiazepine use

BACKGROUND: Psychomotor studies suggest that commonly prescribed psychoactive drugs impair driving skills. We have examined the association between the use of psychoactive drugs and road-traffic accidents. METHODS: We used dispensed prescribing as a measure of exposure in a within-person case-crossover study of drivers aged 18 years and over, resident in Tayside, UK, who experienced a first road-traffic accident between Aug 1, 1992, and June 30, 1995, and had used a psychoactive drug (tricyclic antidepressant, benzodiazepine, selective serotonin-reuptake inhibitor, or other psychoactive drug [mainly major tranquillisers]) between Aug 1, 1992, and the date of the accident. For each driver, the risks of having a road-traffic accident while exposed and not exposed to a drug were compared. FINDINGS: 19386 drivers were involved in a first road-traffic accident during the study period. 1731 were users of any study drug. On the day of the accident, 189 individuals were taking tricyclic antidepressants (within-patient exposure odds ratio for an accident 0.93 [95% CI 0.72-1.21]), 84 selective serotonin-reuptake inhibitors (0.85 [0.55-1.33]), 235 benzodiazepines (1.62 [1.24-2.12]), and 47 other psychoactive drugs (0.88 [0.62-1.25]). The risk associated with benzodiazepine use decreased with increasing driver's age and was greater when the breath test for alcohol was positive. A dose-response relation was evident with benzodiazepines. The increased risk with benzodiazepines was significant for long-half-life drugs, used as anxiolytics, and for short-half-life hypnotics (all zopiclone). INTERPRETATION: Users of anxiolytic benzodiazepines and zopiclone were at increased risk of experiencing a road-traffic accident. Users of anxiolytic benzodiazepines and zopiclone should be advised not to drive.     

Pharmaceutic regulation and inadequate drug prescription in Canada: the case of psychotropic drugs in the 1960s and early 1970s

The outcome of the drug approval process plays a major role in determining how drugs will be prescribed in Canada. The objective of this paper is to examine the nature of the regulatory approval process, its decisions, how these are expressed in pharmaceutical promotion and the ultimate impact of these factors on the prescribing of psychotropic drugs in general and particularly with regard to the benzodiazepines. There is strong circumstantial evidence that the benzodiazepines were approved on the basis of inadequate clinical trials resulting in these drugs being indicated for conditions for which they were not useful and significant safety issues being ignored. These deficiencies in the regulatory process were magnified in the advertising of these products to physicians, thus contributing to inappropriate prescribing in four areas: prescribing for psychosocial problems, overprescribing for somatic complaints, overprescribing to women and overprescribing for anxiety disorders. Problems in the approval process continue to exist and these will manifest themselves in ongoing inappropriate prescribing of psychotropic, and other, medications.     

Antidepressant overdoses and resultant emergency department services: the impact of SSRIs

Suicide is a major source of morbidity and mortality in patients with mental illness. The selective serotonin reuptake inhibitors (SSRIs) and other newer nontricyclic antidepressants appear to have less clinically significant toxicity in overdose, resulting in lower costs of treatment when compared with tricyclic antidepressant (TCA) overdoses. The resource utilization and cost of treatment for SSRI overdoses may not be less if (1) these agents are commonly ingested with other potentially toxic substances, or (2) health care practices have not changed in response to the apparent greater safety of SSRIs. This study evaluates demographic variables of antidepressant overdoses to determine whether differences exist in treatments and monitoring. Additionally, this study evaluates costs associated with care and the impact of co-ingestants on those same factors.     

Fluoxetine tenth anniversary update: the progress continues

This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depression, patients with eating disorders, and patients with obsessive-compulsive disorder (OCD); its long-term (maintenance) efficacy; its side effects and toxicity; and pharmacoeconomic considerations are reviewed. Pharmacotherapy is currently the only proven method for treating major depressive disorder that is applicable to all levels of severity of major depressive illness. Since its introduction 10 years ago, fluoxetine has been available to psychiatrists, primary care physicians, and other nonpsychiatric physicians as full-dose effective pharmacotherapy for patients with depression. Fluoxetine has been widely prescribed by physicians knowledgeable in pharmacology and in the treatment of depression because of its proven efficacy (ie, equal to that of tricyclic antidepressants [TCAs]), its ease of administration (with full therapeutic dosing usually starting from day 1), its generally benign side-effect profile, its remarkable safety in over-dose, and its proven effectiveness in the most common depressed patient population--anxious, agitated, depressed patients--as well as in patients with various subtypes and severities of depression. In more recent years it has also proved effective in the treatment of bulimia, an entity for which only limited or inadequate treatment options had been previously available. In OCD, fluoxetine, with its more acceptable side-effect profile and greater ease of dosing, presents a favorable alternative to previous drug therapy and is useful in treating both obsessions and compulsions. Fluoxetine is currently recognized among clinicians as efficacious in treating anxiety disorders and is being used successfully in special depressed populations such as patients with medical comorbidity, elderly patients, adolescents, and children. Rapid discontinuation or missed doses of short-half-life selective serotonin reuptake inhibitors, TCAs, and heterocyclic antidepressants are associated with withdrawal symptoms of a somatic and psychological nature, which cannot only be disruptive, but can also be suggestive of relapse or recurrence of depression. In striking contrast to these short-half-life antidepressants, fluoxetine is rarely associated with such sequelae on sudden discontinuation or missed doses. This preventive effect against withdrawal symptoms on discontinuation of fluoxetine is attributed to the unique extended half-life of this antidepressant. Current studies show that the overall increased effectiveness of fluoxetine in treating depression compensates for its higher cost, compared with older drugs, by reducing the need for physician contact because of increased compliance and less need of titration, and by reducing premature patient discontinuation, thereby yielding fewer relapses, less recurrence, and less reutilization of mental health services.     

Management of the depressive component of bipolar disorder

Acute bipolar depression (ABD) and breakthrough depression occurring during maintenance therapy of bipolar disorder are associated with significant morbidity and an increased risk of suicide. Lithium is an effective mood stabilizer for ABD, but its onset of antidepressant action is slow and additional antidepressant therapy is often prescribed. The extent to which other mood stabilizers (e.g., carbamazepine and valproate) have antidepressant activity is unclear. Preliminary initial research suggests three potential advantages that selective serotonin reuptake inhibitors have over tricyclic antidepressant for ABD: possibly greater efficacy, fewer adverse effects, and a lower frequency of antidepressant-induced mania. Bupropion may also have significant advantages. However, further research is needed to confirm these findings. Monoamine oxidase inhibitors are the antidepressant of choice for atypical bipolar depression. Electroconvulsive therapy (ECT) has the highest response rate of all treatments for ABD. Further research is needed to explore combination treatments with mood stabilizers and antidepressants for the effective treatment of ABD.