This retrospective analysis of electrocardiographic (ECG) data investigated the cardiovascular effects of paroxetine 10-50 mg/day in pediatric patients (7-18 years of age). Data were collected from three 8- to 10-week, randomized, placebo-controlled, double-blind trials of paroxetine in pediatric patients with major depressive disorder or obsessive-compulsive disorder.
Electrocardiograms (ECGs) were retrospectively retrieved from 63 study sites in the United States and Canada. Only patients with at least one screening and one on-treatment ECG were included. ECGs were analyzed for heart rate, QT interval corrected using Bazett's formula (QTcB) and Fridericia's formula (QTcF), at screening and while being treated. PR, R-R, and QRS intervals and the maximum change in QTcB and QTcF from screening to endpoint were determined. Clinically significant thresholds were defined a priori.
A total of 1,451 ECGs from 449 patients receiving placebo (n = 207), paroxetine (n = 200), or imipramine (n = 42) were analyzed. Treatment with paroxetine did not significantly increase QTcB or QTcF or any ECG parameters compared with placebo. Treatment with imipramine significantly increased heart rate and QTcB, R-R, and QRS intervals compared with either paroxetine or placebo.
Data from this retrospective study indicate that paroxetine (10-50 mg/day) is unlikely to be associated with significant ECG changes in medically healthy pediatric patients.
Panic disorder with or without agoraphobia (PD/A) is common and can be treated effectively with selective serotonin reuptake inhibitor (SSRI) medication or cognitive-behaviour therapy (CBT). However, the lack of access to CBT services has motivated the development of self-help approaches requiring less therapist contact. A novel treatment modality in this field, showing efficacy in several randomized trials but until now not evaluated within the context of regular psychiatric care, is Internet-based treatment. The aim of the present study was to evaluate the effectiveness of Internet-based CBT for patients in a psychiatric setting. Twenty consecutively referred patients with PD were included in the study. A structured clinical interview with a psychiatrist was conducted for inclusion, as well as at post-treatment and at the 6-month follow-up. The treatment consisted of a 10-week CBT-based self-help programme, including minimal therapist support by e-mail. At post-treatment, 94% of patients no longer met DSM-IV criteria for PD (82% at 6-month follow-up). The within-group effect sizes (for the main outcome PDSS; Panic Disorder Severity Scale) were Cohen's d=2.5 (pre- to post-treatment) and 2.8 (pre-treatment to follow-up), respectively. The proportion of responders on the PDSS was 75% at post-treatment and 70% at 6-month follow-up. The results supports earlier efficacy data on Internet-based CBT for PD and indicates that it is effective also within a regular psychiatric setting. However, a larger randomized controlled trial should be conducted, directly comparing Internet-based CBT with traditionally administered CBT within such a setting.
OBJECTIVE: To explore a possible temporal association between changes in antidepressant sales and suicide rates in different age groups. METHODS: A time series analysis using a two-slope model to compare suicide rates in Sweden before and after introduction of the selective serotonin reuptake inhibitors, SSRIs. RESULTS: Antidepressant sales increased between 1977-1979 and 1995-1997 in men from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly as in the 25-44-year-olds and eight times that in the 15-24-year-olds. During the same time period suicide rates decreased in men from 48.2 to 33.3 per 10(5) inhabitants/year and in women from 20.3 to 13.4. There was significant change in the slope in suicide rates after the introduction of the SSRI, for both men and women, which corresponds to approximately 348 fewer suicides during 1990-1997. Half of these 'saved lives' occurred among young adults. CONCLUSION: We demonstrate a statistically significant change in slope in suicide rates in men and women that coincided with the introduction of the SSRI antidepressants in Sweden. This change preceded the exponential increase in antidepressant sales.
BACKGROUND: Major depressive disorder is the second leading cause of disability-adjusted life-years in developed regions of the world and antidepressants are the third-ranking therapy class worldwide. AIMS: To test the public health impact of the escalating sales of antidepressants. METHOD: Nationwide data from Iceland are used as an example to study the effect of sales of antidepressants on suicide, disability, hospital admissions and out-patient visits. RESULTS: Sales of antidepressants increased from 8.4 daily defined doses per 1000 inhabitants per day in 1975 to 72.7 in 2000, which is a user prevalence of 8.7% for the adult population. Suicide rates fluctuated during 1950-2000 but did not show any definite trend. Rates for out-patient visits increased slightly over the period 1989-2000 and admission rates increased even more. The prevalence of disability due to depressive and anxiety disorders has not decreased over the past 25 years. CONCLUSIONS: The dramatic increase in the sales of antidepressants has not had any marked impact on the selected public health measures. Obviously, better treatment for depressive disorders is still needed in order to reduce the burden caused by them.
To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia.
Retrospective register-based cohort study using nationwide registers from 1998 to 2012.
The North Denmark Region.
In total, 638 352 individuals were included.
Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models.
An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14).
All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.
Notes
Cites: J Bone Miner Res. 2011 Aug;26(8):1822-821381111
Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear.
To determine whether there is an association between stress-related disorders and subsequent autoimmune disease.
Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106?464 exposed patients with stress-related disorders, with 1?064?640 matched unexposed persons and 126?652 full siblings of these patients.
Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions.
Stress-related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors.
The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population- and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (=3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at =33, 34-41, 42-50, and =51 years, respectively; P for interaction?
Catechol-O-methyltransferase val108/158met genotype, major depressive disorder and response to selective serotonin reuptake inhibitors in major depressive disorder.
The functional val108/158met polymorphism of the COMT gene (rs4680) was evaluated in major depressive disorder (MDD), and in the treatment response to antidepressants in MDD. We could not demonstrate any significant difference in the distribution of this COMT single-nucleotide polymorphism (SNP) in the treatment response to selective serotonin reuptake inhibitors or between patients with MDD and control subjects.
In this study, the authors analyze how younger women see themselves within the context of using the antidepressants selective serotonin re-uptake inhibitors (SSRIs). Twelve in-depth interviews and 6 reinterviews were conducted with a community-based sample of women who had been taking SSRIs between 1 and 4 years. The empirical analysis revealed that SSRI users passed through stages in their careers as medicine users, these stages corresponding to how the users thought and felt about themselves. Four major changes in self-concept emerged: distressed and needing help, conflicts about taking the medicine, improvements in condition, and problems discontinuing the medicine. Users evaluated themselves from what they believed was the perspective of society, and the way they saw themselves was closely related to how they felt they functioned in everyday life.
OBJECTIVE: Nonhormonal treatment of postmenopausal symptoms is a subject of great interest today. The results of studies on selective serotonin reuptake inhibitors (SSRIs) are promising, but long-term results do not exist. The objective of this study was to evaluate the efficacy of citalopram and fluoxetine in the treatment of physical and psychological menopausal symptoms and their effects on psychosocial and sexual well being in symptomatic postmenopausal women. DESIGN: One hundred fifty healthy women suffering from menopausal symptoms were recruited to this placebo-controlled double-blind study with a follow-up period of 9 months. They were randomized into three groups receiving placebo, fluoxetine, or citalopram. The initial dose was 10 mg of both fluoxetine and citalopram, and it was increased to 20 mg at 1 month and to 30 mg at the 6-month visit. The main outcome measures were hot flushes and Kupperman index. The RAND-36 Quality of Life questionnaire, Beck's Depression Scale, and the McCoy Female Sexuality Questionnaire were used at every control visit. RESULTS: There were no statistically significant differences between the groups in respect to number of hot flushes, Kupperman index, or Beck's Depression Scale, although there was a tendency in all these parameters in favor of SSRIs versus placebo. Insomnia improved significantly in the citalopram group versus placebo. Discontinuation rates at nine months were 40% in the placebo group, 34% in the fluoxetine group and 34% in the citalopram group. CONCLUSIONS: Compared with placebo, citalopram and fluoxetine have little effect on hot flushes and cannot therefore be recommended for the treatment of menopausal symptoms, if vasomotor symptoms are the main complaint. Whether the improvement of insomnia by means of citalopram affects the quality of sleep needs further investigation.
