Increased risk of treatment with antidepressants in stroke compared with other chronic illness

The prevalence of depression and anxiety is higher in patients with stroke than in the general population but it is unclear whether patients with stroke are at an increased risk of being treated for depression and anxiety compared with patients with other chronic illness. The objective of the present study was to investigate whether the rate of treatment with antidepressants is increased in patients with stroke compared with patients with other chronic illness and compared with the general population. By linkage of nationwide case registers, all patients who received a main diagnosis of stroke or osteoarthritis at their first ever admission or first outpatient contact during the period from 1995 to 2001 in Denmark were identified, and the rates of subsequent purchase of antidepressants were calculated. In total, 9,999 patients with a main first diagnosis of stroke and 12,127 patients with a main first diagnosis of osteoarthritis were included. In all, 23.6% of patients with stroke and 9.1% of patients with osteoarthritis purchased antidepressants during follow-up. Patients who received a first diagnosis of stroke had a 3.44 (95% confidence interval: 3.19-3.70) times increased rate of subsequently purchasing antidepressants compared with patients with a first diagnosis of osteoarthritis. The rate was increased in all subgroups of patients regardless of sex, age, socioeconomic group and time since diagnosis. Furthermore, the rate of treatment was greater than the rate among a sex, age and calendar-matched sample of the general population. It is concluded that stroke is associated with an increased rate of antidepressant treatment in clinical practice regardless of sex, age, socioeconomic group and time since diagnosis.     

An observational nationwide register based cohort study on lamotrigine versus lithium in bipolar disorder

It is not clear whether the effectiveness of lamotrigine versus lithium differs for patients with bipolar disorder treated in clinical practice. We compared rates of switch to, or add on of, another psychotropic, and rates of psychiatric hospitalization for patients treated with lamotrigine or lithium in clinical practice. Using linkage of nationwide Danish registers we identified 730 patients who received lamotrigine and 3518 patients received lithium subsequent to a diagnosis of bipolar disorder in psychiatric hospital settings during a period from 1995 to 2006. The overall rate of switch to or add on of another psychotropic (the opposite drug of interest (lithium or lamotrigine), antidepressants, antipsychotics or other anticonvulsants than lamotrigine) was increased for lamotrigine compared with lithium (HR?=?2.60, 95% CI: 2.23-3.04), regardless of whether the index episode was depressive, manic, mixed or remission. In addition, the overall rate of psychiatric hospitalization was increased for lamotrigine compared with lithium (HR?=?1.45, 95% CI: 1.28-1.65), as were the rates for patients with a depressive (HR?=?1.31, 95% CI: 1.01-1.70) and patients with a manic (HR?=?1.65, 95% CI: 1.31-2.09) index episode. Rates did not differ significantly between the drugs for patients with a mixed index episode and for patients in remission. It is concluded that in daily clinical practice, treatment with lithium is in general superior to treatment with lamotrigine.     

Predictors of excellent response to lithium: results from a nationwide register-based study

The aim of this study was to identify sociodemographic and clinical predictors of excellent response, that is, 'cure' of future affective episodes, to lithium in monotherapy. We used nationwide registers to identify all patients with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed lithium from 1995 to 2006 in Denmark (N=3762). Excellent lithium responders were defined as patients who after a stabilization lithium start-up period of 6 months, continued lithium in monotherapy without getting hospitalized. The rate of excellent response to lithium in monotherapy was 8.9% [95% confidence interval (CI): 7.9-9.9] at 5-year follow-up and 5.4% (95% CI: 4.4-6.3) at 10-year follow-up. The rate of nonresponse to lithium monotherapy was significantly increased for female patients [hazards ratio (HR)=1.12, 95% CI: 1.04-1.21) and for patients with a depressive index episode compared with patients in remission or with a diagnosis of other or unspecified bipolar disorder before first lithium purchase (HR=1.13, 95% CI: 1.03-1.25). The rate of nonresponse increased by 3% (95% CI: 2-5%) for every psychiatric hospitalization before first purchase of lithium. Patients with somatic comorbidity had increased rates of non-response to lithium compared with patients without somatic comorbidity (HR=1.23, 95% CI: 1.00-1.52).It is concluded that the prevalence of excellent response to lithium monotherapy is low and such patients are characterized by few earlier psychiatric hospitalizations, a manic index episode before lithium and reduced somatic comorbidity.     

Depression and treatment with antidepressants are associated with the development of gastro‐oesophageal reflux disease

Aliment Pharmacol Ther 31 , 1132–1140

Summary

Background The roles of depression and antidepressants in triggering reflux symptoms remain unclear. Aim To compare the incidence of gastro‐oesophageal reflux disease (GERD) in individuals with and without a depression diagnosis and to evaluate risk factors for a GERD diagnosis. The relationship between antidepressant treatment and GERD was also assessed. Methods The Health Improvement Network UK primary care database was used to identify patients with incident depression and an age‐ and sex‐matched control cohort with no depression diagnosis. Incident GERD diagnoses were identified during a mean follow‐up of 3.3 years. Furthermore, we performed nested case‐control analyses where odds ratios (OR) with 95% confidence intervals (CI) were estimated by unconditional logistic regression in multivariable models. Results The incidence of GERD was 14.2 per 1000 person‐years in the depression cohort and 8.3 per 1000 person‐years in the control cohort. The hazard ratio of GERD in patients with depression compared with controls was 1.72 (95% CI: 1.60–1.85). Among patients with depression, tricyclic antidepressant use was associated with an increased risk of GERD (OR: 1.71; 95% CI: 1.34–2.20), while selective serotonin reuptake inhibitors were not associated with GERD. Conclusions A depression diagnosis is associated with an increased risk of a subsequent GERD diagnosis, particularly in individuals using tricyclic antidepressants.     

Efficacy of statins in combination with interferon therapy in multiple sclerosis: A meta-analysis

Purpose The efficacy of statins in combination with interferon therapy in patients with multiple sclerosis (MS) is reviewed. Methods A systematic literature search was conducted through September 2011 to identify randomized controlled trials that evaluated the effect of combination statin-interferon therapy compared with interferon therapy alone in patients with MS. Trials had to report at least one of the following outcomes of interest: clinical relapse rate, disease progression, or Expanded Disability Status Scale (EDSS) score. A random-effects model was used to pool data. Trial quality was assessed using the Jadad score. Results Four unique trials were included in the analysis (n = 463 subjects; range of follow-up, 9-24 months), all with a Jadad score of ≥3. All trials evaluated patients with relapsing-remitting MS (RRMS). Most trials enrolled patients taking interferon beta therapy either twice or three times weekly. The mean baseline EDSS scores ranged from 1.2 to 3.4. Evaluated statins included simvastatin and atorvastatin. No significant difference was found between the statin and control groups in the incident rate ratio for clinical relapse (0.72; 95% confidence interval [CI], 0.17 to 3.11), risk of relapse (relative risk [RR], 0.99; 95% CI, 0.53 to 1.85], disease progression (RR, 1.31; 95% CI, 0.73 to 2.36), or difference in the change in the EDSS score from baseline (weighted mean difference, -0.06; 95% CI, -0.30 to 0.19). Conclusion A meta-analysis revealed that the addition of statins to interferon therapy did not significantly influence the relapse risk, disease progression, or EDSS scores in patients with RRMS.     

Patients' concerns about and problems experienced with discontinuation of antidepressants

Objective Clinical trials and epidemiological studies have shown that premature discontinuation is a major problem during antidepressant therapy. Unfortunately, there is little information on how patients perceive treatment with antidepressants in clinical practice, and it is unclear whether patients perceive discontinuation as a problem. The objective of this study is to assess whether concerns and problems experienced with drug discontinuation occur more frequently in patients using antidepressants than in patients using benzodiazepines, antipsychotics or non‐psychiatric medication. Method All calls to a national telephone medicines information service received between 1990 and 2004 were examined using retrospective examination. Calls about discontinuation were identified and classified either as a general question about discontinuation, or as a problem experienced with discontinuation. These calls were grouped into the following main classes: antidepressants, antipsychotics, benzodiazepines or non‐psychiatric medicines. Key findings Of all 39 786 registered phone calls, 6159 (15,5%) related to antidepressants, 1658 (4.2%) to antipsychotics and 3916 (9.8%) to benzodiazepines. Patients calling about antidepressants called about discontinuation three times as often (odds ratio (OR) 2.8; 95% confidence interval (CI) 2.6–3.0), and reported a problem with discontinuation five times more often (OR 5.4; 95% CI 4.6–6.3), compared to patients who called about non‐psychiatric medicines. The proportion of questions about discontinuation and problems experienced with discontinuation was also higher in patients calling about benzodiazepines and antipsychotics compared to patients calling about non‐psychiatric medication. Conclusion Patients perceive discontinuation of antidepressants, as well as discontinuation of antipsychotics and benzodiazepines, as a problem. Discontinuation seems a general problem for all psychiatric medicines, and needs more attention in the communication between patients and healthcare providers.     

Influence of initial use of serotonergic antidepressants on antiparkinsonian drug use in levodopa-using patients

OBJECTIVE: To assess whether there is an association between initial use of serotonergic antidepressants and changes in antiparkinsonian drug treatment. METHODS: A retrospective cohort study was performed with the PHARMO record linkage system. All patients from 1994 until 2004 of 40 years or older who were first time users of an antidepressant and who had used a levodopa-containing drug at least 180 days before initiation of the antidepressant were included. The maximum follow-up time was 180 days. The first change in antiparkinsonian drug treatment, defined as an increase in the daily dosage of any antiparkinsonian drug, the start of a new antiparkinsonian drug or a change in the dosage form during the follow-up period, was taken as an endpoint. Antidepressants were classified in two ways: according to their class [selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) or other antidepressants] or by the extent of their inhibition of serotonin reuptake (high, intermediate or low). RESULTS: A total of 221 patients was included in our study. The adjusted hazard ratio for a change in antiparkinsonian drug treatment was 0.7 (95% CI 0.3-1.5) comparing SSRI with TCA users, and it was 0.9 (95% CI 0.4-2.1) comparing users of other antidepressants with TCA users. The adjusted hazard ratio for a change in antiparkinsonian drug treatment was 0.6 (95% CI 0.3-1.4) comparing users of antidepressants with high versus low extent of inhibition of serotonin reuptake, and it was 0.7 (95% CI 0.3-1.4) comparing users of antidepressants with intermediate versus low extent of inhibition of serotonin reuptake. CONCLUSION: Based on these observations, we found no evidence to be more cautious using SSRIs or serotonergic antidepressants compared to other antidepressants in patients with Parkinson's disease.     

The interaction of saquinavir (soft gelatin capsule) with ketoconazole, erythromycin and rifampicin: comparison of the effect in healthy volunteers and in HIV-infected patients

OBJECTIVE: The aim of this study was to compare the effect of ketoconazole, erythromycin and rifampicin on the pharmacokinetics of saquinavir soft-gelatin formulation (Fortovase; FTV) in healthy volunteers with that in HIV-infected patients at steady state after administration of 1200 mg three times daily. METHODS: In two open-labelled, randomised, crossover studies pharmacokinetic parameters were calculated in healthy volunteers who received on one occasion multiple doses of 1200 mg FTV three times daily alone and on the other occasion in combination with multiple doses of either 400 mg ketoconazole once daily or 600 mg rifampicin once daily. In another open-labelled, multicentre study, 33 HIV-infected patients underwent a pharmacokinetic assessment after 36-51 weeks of treatment with FTV and were then given additionally multiple doses of either 200 mg ketoconazole once daily, 250 mg erythromycin four times daily or 600 mg rifampicin once daily. Pharmacokinetic parameters of saquinavir were determined again at the end of the combination treatment. RESULTS: In healthy volunteers, coadministration of ketoconazole increased saquinavir area under the curve from time 0 to 8 h (AUC0-8 h) by 190% (95% CI: 90-343) whereas coadministration with rifampicin resulted in a decrease for AUC0-8 h by 70% (95% CI: 50-82). In HIV-infected patients, coadministration of ketoconazole and erythromycin increased AUC0-8 h of saquinavir by 69% (95% CI: 14-150) and 99% (95% CI: 33-198), respectively. When saquinavir was given together with rifampicin, exposure of saquinavir in terms of AUC0-8 h was decreased by 46% (95% CI: 18-65) compared with the baseline assessment. CONCLUSION: Interactions of saquinavir with ketoconazole, erythromycin and rifampicin were observed in healthy volunteers as well as patients. The effects observed in patients, however, appear to be less pronounced. The enzyme induction caused by rifampicin might lead to subtherapeutic levels of saquinavir and this finding appears to be of clinical relevance.     

Pregnancy outcome after exposure to antidepressants and the role of maternal depression: results from the Norwegian Mother and Child Cohort Study

Results of previous studies on the safety of antidepressants during pregnancy have been conflicting. The primary objective of this study was to investigate whether first-trimester exposure to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), was associated with increased risk of congenital malformations. The secondary objective was to examine the effects of exposure to antidepressants during pregnancy on birth weight and gestational age.We included 63,395 women from the Norwegian Mother and Child Cohort Study. The women had completed 2 self-administered questionnaires at gestational weeks 17 and 30 on medication use and medical, sociodemographic, and psychological factors. Data on pregnancy outcome were retrieved from the Medical Birth Registry of Norway.Of the 63,395 women, 699 (1.1%) reported using antidepressants during pregnancy, most frequently SSRIs (0.9%). Exposure to SSRIs during the first trimester was not associated with increased risk of congenital malformations in general (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 0.81-1.84) or cardiovascular malformations (adjusted OR, 1.51; 95% CI, 0.67-3.43). Exposure to antidepressants during pregnancy was not associated with increased risk of preterm birth (adjusted OR, 1.21; 95% CI, 0.87-1.69) or low birth weight (adjusted OR, 0.62; 95% CI, 0.33-1.16).This study does not suggest a strongly increased risk of malformations, preterm birth, or low birth weight following prenatal exposure to antidepressants. Without adjustments for level of maternal depression and various sociodemographic and lifestyle factors, antidepressant use during pregnancy would wrongly have been associated with an increased risk of preterm birth.     

Benefits and risks of pharmacotherapy for dysthymia: a systematic appraisal of the evidence.

BACKGROUND: Dysthymia is a prevalent form of subthreshold depressive disorder, associated with considerable disability and high co-morbidity. This paper systematically appraises the evidence for the efficacy and acceptability of the pharmacological treatment for this condition. METHODS: Randomised, controlled trials evaluating the efficacy of drug therapies for dysthymia were included. A comprehensive search of the literature was performed, aiming to avoid publication bias. Pooled relative risks (RR) and 95% CIs were calculated with the Random Effect Model method. The number needed to treat (NNT) and number needed to harm (NNH) were estimated for statistically significant results. RESULTS: Twenty-five trials were included for the main comparisons. Regarding placebo-controlled trials (n = 16), similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other drugs (sulpiride, amineptine, and ritanserin). The pooled RR for treatment response was 0.68 (95% CI 0.57-0.81) for TCA and the NNT was 4.3 (95% CI 3.2-6.5); 0.68 (95% CI 0.56-0.82) for SSRIs (NNT 5.1; 95% CI 3.9-7.7); 0.59 (95% CI 0.48-0.71) for MAOIs (NNT 2.9; 95% CI 2.2-4.3). Other drugs (amisulpride, amineptine and ritanserin) showed similar results. The equivalent efficacy between antidepressants as found in trials where active medications were compared confirmed the efficacy findings from placebo trials. In general, patients treated with a TCA were more likely to report adverse events, compared with placebo and SSRIs. CONCLUSIONS: Pharmacotherapy for dysthymia appears to be an effective short-term treatment for dysthymic disorder. Newer antidepressants are equally effective and have better acceptability than TCAs, although their higher cost must be balanced against this assumed advantage.     

The Association Between Stimulant,Opioid, and Multiple Drug Use on Behavioral Health Care Utilization in a Safety-Net Health System

Background: Prior studies show an association between drug use and health care utilization. The relationship between specific drug type and emergent/urgent, inpatient, outpatient, and behavioral health care utilization has not been examined. We aimed to determine if multiple drug use was associated with increased utilization of behavioral health care. Methods: To assess health care utilization, we conducted a retrospective cohort study of patients who accessed health care at a safety-net medical center and affiliated clinics. Using electronic health records, we categorized patients who used stimulants, opioids, or multiple drugs based on urine toxicology screening tests and/or International Classification of Diseases, 9th Revision (ICD-9). Remaining patients were categorized as patients without identified drug use. Health care utilization by drug use group and visit type was determined using a negative binomial regression model. Associations were reported as incidence rate ratios. Utilization was described by rates of health care–related visits for inpatient, emergent/urgent, outpatient, and behavioral health care among patients who used drugs, categorized by drug types, compared with patients without identified drug use. Results: Of 95,198 index visits, 4.6% (n = 4340) were by patients who used drugs. Opioid and multiple drug users had significantly higher rates of behavioral health care visits than patients without identified drug use (opioid incidence rate ratio [IRR] = 7.2; 95% confidence interval [CI]: 3.8–13.8; multiple drug use IRR = 5.6, 95% CI: 3.3–9.7). Patients who used stimulants were less likely to use behavioral health services (IRR = 1.3, 95% CI: 0.9–2.0) when compared with opioid and multiple drug users, but were more likely to use inpatient (IRR = 1.6, 95% CI: 1.4–1.8) and emergent/urgent care (IRR = 1.4, 95% CI: 1.3–1.5) services as compared with patients without identified drug use. Conclusions: Integrated medical and mental health care and drug treatment may reduce utilization of costly health care services and improve patient outcomes. How to capture and deliver primary care and behavioral health care to patients who use stimulants needs further investigation.