OBJECTIVE: The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) are extensively used in the treatment of depression, panic disorder and obsessive-compulsive disorder, and are now being evaluated in the treatment of a number of other psychiatric disorders. The aim of this study was to investigate the pattern of adverse reactions reported on SSRIs in Sweden and assess possible risk factors associated with the occurrence of adverse reactions to these agents. METHODS: A survey was made of 1202 reports describing 1861 adverse reactions to SSRIs submitted to the Swedish Adverse Drug Reactions Advisory Committee. RESULTS: The most often reported adverse reactions were neurological symptoms (22.4%), psychiatric symptoms (19.5%) and gastrointestinal symptoms (18.0%); however, dermatological symptoms (11.4%) and general symptoms (9.8%) were also frequent. Compared with other drugs, gastrointestinal symptoms were more often reported for fluvoxamine, psychiatric symptoms were more often reported for sertraline and dermatological symptoms were more often reported for fluoxetine. In total, the diagnoses most frequently reported were nausea (n = 139), rash (n = 90), anxiety (n = 84), paraesthesias (n = 69), headache (n = 63) and diarrhoea (n = 63). Parkinsonism, confusion, hallucinations, euphoria, hyponatraemia, bradycardia and hypotension were more often reported in the elderly, whereas urticaria, akathisia, and haematological, endocrinological, sexual and some visual reactions were more often reported in individuals who were younger than average. Dermatological reactions, fatigue, hyponatraemia and cough were more common in women, whereas dyskinesias/akathisia and aggression more often were seen in men. The median SSRI dosages were above average in patients experiencing seizures, hypomania/mania, personality changes, malaise, bodyweight gain, gynaecomastia and hyperprolactinaemia/galactorrhoea. Severe symptoms, such as seizures, hyponatraemia and the serotonin syndrome, were rarely reported. CONCLUSION: Although the design of the study makes it difficult to draw conclusions about causality, a variety of adverse reactions were reported. Therefore, the awareness that a particular symptom in a patient treated with an SSRI might be an adverse reaction should be high.
PURPOSE: To study the association between alopecia and selective serotonin reuptake inhibitors (SSRIs) by estimating reporting rates and by making association comparisons within databases of adverse drug reactions (ADRs). METHODS: All reports of alopecia with marketed SSRIs until the end of 2004 were identified in SWEDIS, the national Swedish database for spontaneously reported ADRs, and in Vigibase, the international ADR database of the World Health Organization. Total SSRI sales volumes in Sweden until the end of 2004 were obtained from the National Corporation of Swedish Pharmacies. The Bayes' Confidence Propagation Neural Network (BCPNN) method was used to estimate associations between alopecia and each of the SSRIs within the two databases. RESULTS: A total of 27 reports of alopecia were identified in SWEDIS. As two reports concerned the use of two SSRIs, there was a total of 29 drug-ADR combinations. All except three reports concerned women (88.9%). The reporting rate of alopecia in Sweden was significantly higher with sertraline compared with citalopram; 20.1 (95%CI 10.7-34.4) reports per million patient-years versus 4.5 (95%CI 1.8-9.3) reports per million patient-years. No significant differences in reporting rates were noted for the remaining SSRIs. Sertraline also showed a statistically significant association with alopecia in both SWEDIS and Vigibase. Citalopram was significantly associated with alopecia in Vigibase, but not in SWEDIS. No statistically significant associations were found for any of the other SSRIs. CONCLUSIONS: Alopecia appears to be a rare ADR to SSRIs. The risk of alopecia seems to vary between the different SSRIs, and might be higher in women than in men.
Recent reports suggest that adverse effects on sexual function occur in up to 50% of patients who are treated with selective serotonin reuptake inhibitor (SSRI) antidepressants. Previously cited low rates were more likely a function of underreporting than underoccurrence. There is less evidence about rates of dysfunction with serotonin-norepinephrine reuptake inhibitor (SNRI) and reversible inhibitor of monoamine oxidase A (RIMA) antidepressants. The purpose of this report is to evaluate disturbances in sexual drive/desire and arousal/orgasm in 107 patients who met criteria for major depressive disorder and received treatment with either moclobemide, paroxetine, sertraline, or venlafaxine.
All consenting eligible patients who met DSM-IV criteria for major depressive disorder completed the Sexual Functioning Questionnaire, version 1 (SFQ) and were assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D) prior to and after 8 or 14 weeks of antidepressant therapy. Analyses were carried out to examine the effect of gender, drug type, pretreatment level of sexual dysfunction, and drug response on reported sexual dysfunction.
Compared with women, men experienced a significantly greater level of drug-related impairment in drive/desire (p
Experimental and epidemiologic studies suggest that antidepressant medication use may be associated with breast cancer risk. This hypothesis was investigated using a population-based case-control study; cases diagnosed in 1995-1996 were identified using the Ontario Cancer Registry, and controls were randomly sampled from an Ontario Ministry of Finance database. Data were collected using a self-administered questionnaire, and multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals. Adjusted odds ratio estimates ranged from 0.7 to 0.8 and were not statistically significant for "ever" use of antidepressants, tricyclics, and selective serotonin reuptake inhibitors. Compared with no antidepressant use, use of tricyclic antidepressants for greater than 2 years' duration was associated with an elevated risk of breast cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI): 0.9, 5.0). Of the six most commonly reported antidepressant medications, only paroxetine use was associated with an increase in breast cancer risk (OR = 7.2, 95% CI: 0.9, 58.3). Results from this study do not support the hypothesis that "ever" use of any antidepressant medications is associated with breast cancer risk. Use of tricyclic medications for greater than 2 years, however, may be associated with a twofold elevation, and use of paroxetine may be associated with a substantial increase in breast cancer risk.
Comment In: Am J Epidemiol. 2000 Dec 1;152(11):1104-511117620
Comment In: Am J Epidemiol. 2000 Dec 1;152(11):1104; author reply 110511117621
PURPOSE: Several studies have found an increased risk of myocardial infarction among depressed patients. Selective serotonin reuptake inhibitors (SSRIs) appear to lack the arrhythmic adverse effects of tricyclic antidepressants, and are thought to inhibit platelet aggregation. We examined whether use of different antidepressant classes is associated with a lower risk of first-time hospitalization for myocardial infarction, as compared with nonuse. METHODS: We identified 8887 cases of first-time hospitalization for myocardial infarction and 88,862 age- and sex-matched population-based controls during 1994-2002, using data from North Jutland County, Denmark. Cases and controls were stratified according to history of cardiovascular disease. All prescriptions for antidepressants before hospitalization for myocardial infarction were identified using a prescription database. Conditional logistic regression was used to estimate odds ratios of myocardial infarction associated with antidepressant use, adjusted for possible confounding factors. RESULTS: In patients with a history of cardiovascular disease, we found indications of a lower risk of myocardial infarction among those who used SSRIs (adjusted odds ratio [OR] = 0.85; 95% confidence interval [CI]: 0.62 to 1.16), nonselective serotonin reuptake inhibitors (adjusted OR = 0.83; 95% CI: 0.50 to 1.38), and other antidepressants (adjusted OR = 0.55; 95% CI: 0.31 to 0.97). There were no such associations among persons without a history of cardiovascular disease. CONCLUSION: Antidepressant use may be associated with a decreased risk of hospitalization for myocardial infarction among persons with a history of cardiovascular disease, although it remains uncertain whether there are differences by class of antidepressant.
Although the association between antidepressant drug use and risk of cancer has received considerable attention in the past years, no work has been done specifically on prostate cancer. We carried out a population-based case-control study to assess the risk of prostate cancer in association with exposure to tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). 7767 prostate cancer cases diagnosed between 1981 and 2000 were accrued through the Saskatchewan Cancer Agency. Saskatchewan Health identified a total of 31,068 male controls who were matched on age and calendar time. Data on exposure to TCAs and SSRIs were compiled from the Saskatchewan outpatient prescription drug database, and covered a period upto 24 years. A positive significant association was found between TCA use and risk of prostate cancer, when exposure took place 2-5 years before diagnosis, with rate ratios of 1.31, 1.58, and 2.42 at the low, medium and high average daily dose levels, respectively. Exposure to SSRIs was not found to be significantly associated with the risk of prostate cancer. TCA use 2-5 years in the past was associated with a small dose-dependent increase in the risk of prostate cancer. Nevertheless, detection bias could have contributed to the observed association.
It is unknown if antidepressant treatment is associated with either increased or decreased risk of suicide.
To estimate the risk of suicide, attempted suicide, and overall mortality during antidepressant treatments in a real-life setting with high statistical power.
A cohort study in which all subjects without psychosis, hospitalized because of a suicide attempt from January 1, 1997, to December 31, 2003, in Finland, were followed up through a nationwide computerized database.
A total of 15 390 patients with a mean follow-up of 3.4 years.
The propensity score-adjusted relative risks (RRs) during monotherapy with the most frequently used antidepressants compared with no antidepressant treatment.
In the entire cohort, fluoxetine use was associated with the lowest risk (RR, 0.52; 95% confidence interval [CI], 0.30-0.93), and venlafaxine hydrochloride use with the highest risk (RR, 1.61; 95% CI, 1.01-2.57), of suicide. A substantially lower mortality was observed during selective serotonin reuptake inhibitor use (RR, 0.59; 95% CI, 0.49-0.71; P
Comment In: Evid Based Ment Health. 2007 Aug;10(3):9017652572
The present study aimed to investigate prevalence of and reasons for selective serotonin reuptake inhibitor (SSRI) discontinuation, and compare the two most common SSRIs used in premature ejaculation (PE) treatment, in naturalistic settings (that is, outside clinical trials). The sample consisted of 132 Finnish men with a mean age of 42.5 years (s.d. = 10.6) who had received medical treatment for lifelong PE. The men were enlisted for the study after identifying individuals from the third author's (a physician specializing in sexual medicine) patient registry. Participants responded to a secure, online questionnaire. PE treatment-related side effects of, and discontinuation rates for, different SSRIs were retrospectively self-reported. Treatment efficacy and happiness with treatment were retrospectively self-assessed. Discontinuation rates were uniformly high, ranging from 28.8 to 70.6% between different SSRIs. Dapoxetine was associated with the highest dropout rates (70.6%), and paroxetine the lowest, discontinuation rates. Limited efficacy and side effects were the most common reasons for discontinuation. Paroxetine was more effective and better tolerated than dapoxetine. A considerable number of patients chose to spontaneously discontinue treatment, especially so in the case of dapoxetine, corroborating recent studies conducted in naturalistic settings. Further research efforts are necessary to develop new and improve existing PE treatment alternatives.