Combined Selective Serotonin Reuptake Inhibitors Research Articles

Is transcranial direct current stimulation, alone or in combination with antidepressant medications or psychotherapies, effective in treating major depressive disorder? A systematic review and meta-analysis

BackgroundTranscranial direct current stimulation (tDCS) has shown mixed results for depression treatment. The efficacies of tDCS combination therapies have not been investigated deliberately. This review aims to evaluate the clinical efficacy of tDCS as a monotherapy and in combination with medication, psychotherapy, and ECT for treating adult patients with major depressive disorder (MDD) and identified the factors influencing treatment outcome measures (i.e. depression score, dropout, response, and remission rates).MethodsThe systematic review was performed in PubMed/Medline, EMBASE, PsycINFO, Web of Sciences, and OpenGrey. Two authors performed independent literature screening and data extraction. The primary outcomes were the standardized mean difference (SMD) for continuous depression scores after treatment and odds ratio (OR) dropout rate; secondary outcomes included ORs for response and remission rates. Random effects models with 95% confidence intervals were employed in all outcomes. The overall effect of tDCS was investigated by meta-analysis. Sources of heterogeneity were explored via subgroup analyses, meta-regression, sensitivity analyses, and assessment of publication bias.ResultsTwelve randomised, sham-controlled trials (active group: N = 251, sham group: N = 204) were included. Overall, the integrated depression score of the active group after treatment was significantly lower than that of the sham group (g = − 0.442, p = 0.017), and further analysis showed that only tDCS + medication achieved a significant lower score (g = − 0.855, p < 0.001). Moreover, this combination achieved a significantly higher response rate than sham intervention (OR = 2.7, p = 0.006), while the response rate remained unchanged for the other three therapies. Dropout and remission rates were similar in the active and sham groups for each therapy and also for the overall intervention. The meta-regression results showed that current intensity is the only predictor for the response rate. None of publication bias was identified.ConclusionThe effect size of tDCS treatment was obviously larger in depression score compared with sham stimulation. The tDCS combined selective serotonin re-uptake inhibitors is the optimized therapy that is effective on depression score and response rate. tDCS monotherapy and combined psychotherapy have no significant effects. The most important parameter for optimization in future trials is treatment strategy.

Can acupuncture combined with SSRIs improve clinical symptoms and quality of life in patients with depression? Secondary outcomes of a pragmatic randomized controlled trial

ObjectivesTo explore the effects of acupuncture (manual acupuncture or electroacupuncture) combined with SSRIs for moderate to severe depression improving major clinical symptoms and life quality of the patients on secondary outcomes. DesignPragmatic, parallel, randomized controlled trial. Setting6 hospitals in China. Interventions6 weeks of manual acupuncture (MA)+selective serotonin reuptake inhibitors (SSRIs), electroacupuncture (EA)+SSRIs, and SSRIs alone. Main outcome measuresThe primary outcome was response rate of 17-item Hamilton Depression Scale (HAMD-17) total score at 6th week. The secondary outcomes reported in this analysis were HAMD-17 factor scores at 1st, 2nd, 4th, 6th, 10th week and WHO Quality of Life-BREF (WHOQOL-BREF) scores at 6th week. Results477 patients were randomly assigned into MA + SSRIs (n = 161), EA + SSRIs (n = 160), or SSRIs alone (n = 156) groups. For HAMD-17 (at 6th week), the MA + SSRIs group was significantly better than the SSRIs alone group in retardation factor (p = 0.008), while the EA+SSRIs group was significantly better than the SSRIs alone group in anxiety/somatization factor (p<0.001) and sleep disturbance factor (p = 0.002). For WHOQOL-BREF (at 6th week), the EA + SSRIs group, compared with the SSRIs alone group, produced a more significant improvement in the overall quality of life, general health, physical health, and psychological health (p<0.05). While, the MA + SSRIs group, compared to the SSRIs alone group, showed significant advantage only in psychological health (p = 0.023). ConclusionsEither MA or EA combined SSRIs treatment could improve symptoms and quality of life for patients with moderate to severe depression. The main limitation of this trial was not using a sham control therefore the placebo effect could not be excluded.

Importance of Proactive Treatment of Depression in Lewy Body Dementias: The Impact on Hippocampal Neurogenesis and Cognition in a Post-Mortem Study

Objective: To examine the impact of selective serotonin reuptake inhibitors (SSRIs) and depression on neurogenesis and cognition in dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). Methods: Late-stage progenitor cells were quantified in the subgranular zone (SGZ) of the hippocampal dentate gyrus of DLB/PDD patients (n = 41) and controls without dementia (n = 15) and compared between treatment groups (unmedicated, SSRIs, acetyl cholinesterase inhibitors [AChEIs], combined SSRIs and AChEIs). Results: DLB/PDD patients had more doublecortin-positive cells in the SGZ compared to controls. The doublecortin-positive cell count was higher in the SGZ of patients treated with SSRIs and correlated to higher cognitive scores. Conclusion: SSRI treatment was associated with increased hippocampal neurogenesis and preservation of cognition in DLB/PDD patients.

Interactions between SSRI's and statins: Clinical relevance versus statistical significance

IntroductionDepression and hypercholesterolemia are two of the most commonly treated conditions in the developed countries, while the lipid–lowering agents and antidepressants are among the most widely prescribed drugs in the world. There is a common concern that selective serotonin reuptake inhibitors (SSRIs) can trigger statin adverse effects, especially myopathy. However, the supporting evidence originates from studies in-vitro and big epidemiological studies. Recent pharmacokinetic insights indicate that the magnitude of pharmacokinetic interaction between SSRIs and statins is likely to be below the threshold for clinical significance.Objectives and aimsExplorative study on pharmacokinetic effects of SSRIs on statin drugs.MethodsWe performed a detailed literature review through PubMed, EMBASE and Cochran's Library to assess the clinical relevance of combined SSRIs and statin use. To address pharmacokinetic interactions between two drug groups, we focused on:– cytochrome P450 enzyme metabolism of statins;– CYP enzyme inhibition by SSRIs;– SSRIs–statin drug interactions;– non-CYP pharmacokinetic pathways.ResultsWith regard to pharmacokinetic drug interactions and the risk of statin related myopathy, escitalopram, citalopram, and paroxetine are to be safe in co-therapy with all statins. Rosuvastatin and pravastatin are almost certain to be safe in co-therapy with all SSRIs. Fluoxetine and sertraline are also likely to be safe, even when combined with atorvastatin, simvastatin, and lovastatin.ConclusionThough the absolute risk of concomitant use of SSRIs with statins seems to be negligible, even this risk can be minimized by using lower statin doses and monitoring the patient.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Rapid Onset of the Effects of Combined Selective Serotonin Reuptake Inhibitors and Electroacupuncture on Primary Depression: A Meta-Analysis.

To evaluate the efficacy and safety of combined selective serotonin reuptake inhibitors (SSRIs) and electroacupuncture therapies for the early treatment of primary depression. Randomized controlled trials (RCTs) were analyzed to compare therapy combining SSRIs and electroacupuncture to SSRI therapy alone. The RCTs were identified by searching, among others, PubMed, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Chongqing VIP database for Chinese Technical Periodicals, WANFANG DATA, and the Chinese Biological Medical Literature Database. Scores from Self-Rated Depression Scale (SDS), the Hamilton Depression Scale (HAMD), the Side Effect Rating Scale (SERS), and the Treatment Emergent Symptom Scale (TESS) were analyzed and coded by two independent investigators and used to evaluate the safety and efficacy of treatment. Statistical analyses were performed using RevMan 5.2 software. Six RCTs were analyzed. The meta-analysis revealed that the combined therapy of SSRIs and electroacupuncture were associated with superior scores on the HAMD, SDS, and SERS measures compared with SSRIs alone after 1-4 weeks of treatment: HAMD scores, mean difference (MD)(1 week), 2.32 (95% confidence interval [CI](1 week), 1.47-3.16, p(1 week)<0.00001); MD(2 weeks), 2.65 (95% CI(2 weeks), 1.81- 3.50, p(2 weeks)<0.00001); MD(4 weeks), 2.70 (95% CI(4 weeks), 1.90-3.51, p(4 weeks)<0.00001); SDS scores: MD(1 week), 3.13 (95% CI(1 week), 1.22-5.03, p(1 week) = 0.001); MD(2 weeks), 4.05 (95% CI(2 weeks), 0.22-7.87, p(2 weeks) = 0.04); MD(4 weeks), 5.02 (95% CI(4 weeks), 1.61-8.43, p(4 weeks) = 0.004); SERS scores: MD(2 weeks), 2.20 (95% CI(2 weeks), 1.43-2.96, p(2 weeks)<0.00001); MD(4 weeks), 2.12 (95% CI(4 weeks), 1.42-2.83, p(4 weeks)<0.00001). However, two of the aforementioned outcomes were rated as medium quality because of heterogeneity, as assessed using the Grading of Recommendations Assessment, Development and Evaluation system. The available evidence suggests that the early treatment of primary depression using both SSRI and electroacupuncture therapies is more efficient than treatments with SSRIs alone and leads to a better and earlier control of depressive symptoms.

Inflammation and depression: combined use of selective serotonin reuptake inhibitors and NSAIDs or paracetamol and psychiatric outcomes.

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol have been shown to yield the potential of adjunctive antidepressant treatment effects to selective serotonin reuptake inhibitors (SSRIs); however, when investigating treatment effects of concomitant use, simultaneous evaluation of potential adverse events is important. The objective was thus to investigate treatment effectiveness and safety aspects of concomitant SSRI use with NSAIDs or paracetamol.MethodsWithin a 25% random sample of the Danish population, we identified all incident SSRI users between 1997 and 2006 (N = 123,351). Effectiveness and safety measures were compared between periods of SSRI use only and periods of combined SSRI and NSAID or paracetamol use by applying Cox regression.ResultsAmong 123,351 SSRI users (follow-up: 53,697.8 person-years), 21,666 (17.5%) used NSAIDs and 10,232 (8.3%) paracetamol concomitantly. Concomitant NSAID use increased the risk of any psychiatric contact [Hazard rate ratio (95%-confidence interval): 1.22 (1.07; 1.38)] and with depression [1.31 (1.11; 1.55)]. Low-dose acetylsalicylic acid reduced the risk of psychiatric contact in general [0.74 (0.56; 0.98)] and with depression [0.71 (0.50; 1.01)]. Ibuprofen reduced the risk of psychiatric contacts [0.76 (0.60; 0.98)]. Concerning safety, paracetamol was associated with increased mortality [3.18 (2.83; 3.58)], especially cardiovascular [2.51 (1.93; 3.28)]. Diclofenac [1.77 (1.22; 2.55)] and the selective COX-2 inhibitors [1.75 (1.21; 2.53)] increased mortality risks.ConclusionsConcomitant use of SSRIs and NSAIDs occurred frequently, and effectiveness and safety outcomes varied across individual NSAIDs. Especially low-dose acetylsalicylic acid may represent an adjunctive antidepressant treatment option. The increased mortality risk of concomitant use of paracetamol needs further investigation.

A population-based case-control study of Selective Serotonin Reuptake Inhibitors (SSRIs) and breast cancer: the impact of duration of use, cumulative dose and latency.

BackgroundSelective serotonin reuptake inhibitors (SSRIs), a popular class of antidepressants, may increase breast cancer risk by stimulating the secretion of prolactin, a potential tumour promoter. We evaluated the effects of duration of SSRI use, cumulative dose, and latency on the risk of breast cancer by conducting a population-based case-control study utilizing Saskatchewan health databases.MethodsCases included 1,701 women with primary invasive breast cancer diagnosed from 2003 to 2006, and controls consisted of 17,017 women, randomly selected from the population registry. Use of SSRIs was compiled using the Saskatchewan prescription database. Unconditional logistic regression was conducted to evaluate the impact of duration of combined SSRI use (total number of prescriptions dispensed), cumulative dose (total dosage received) and timing of use (two or more years, two to seven years and more than seven years prior to index date) on the risk of breast cancer.ResultsOverall, SSRI use was not associated with an increased risk of breast cancer regardless of our definition of cumulative use (total number of prescriptions dispensed and total dosage). In addition, our results indicate that prolonged SSRI use does not have a latent effect on breast cancer risk. Also, our findings are not suggestive of an increased risk of breast cancer with the use of individual SSRIs.ConclusionsOur study improved upon most previous studies by having a longer follow-up period, a larger sample size of long-term SSRI users and consideration of risk during specific exposure time windows that take latency into account. Given the potential health benefits of using SSRIs, our results suggest that the issue of breast cancer risk may no longer be a concern for women requiring long-term SSRIs.

Cost-effectiveness of selective serotonin reuptake inhibitors and routine specialist care with and without cognitive–behavioural therapy in adolescents with major depression

Major depression is an important and costly problem among adolescents, yet evidence to support the provision of cost-effective treatments is lacking. To assess the short-term cost-effectiveness of combined selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy (CBT) together with clinical care compared with SSRIs and clinical care alone in adolescents with major depression. Pragmatic randomised controlled trial in the UK. Outcomes and costs were assessed at baseline, 12 and 28 weeks. The trial comprised 208 adolescents, aged 11-17 years, with major or probable major depression who had not responded to a brief initial psychosocial intervention. There were no significant differences in outcome between the groups with and without CBT. Costs were higher in the group with CBT, although not significantly so (P=0.057). Cost-effectiveness analysis and exploration of the associated uncertainty suggest there is less than a 30% probability that CBT plus SSRIs is more cost-effective than SSRIs alone. A combination of CBT plus SSRIs is not more cost-effective in the short-term than SSRIs alone for treating adolescents with major depression in receipt of routine specialist clinical care.

Differential Antidepressant Symptom Efficacy: Placebo-Controlled Comparisons of Duloxetine and SSRIs (Fluoxetine, Paroxetine, Escitalopram)

Objective: To test the hypothesis that in patients with major depressive disorder (MDD), the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors (SSRIs) and that patterns of response will differ based on symptom severity at baseline. Method: Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD: 7 randomized, double-blind, fixed-dose, 8-week studies of duloxetine (n = 1,133) versus SSRI (n = 689) versus placebo (n = 641). Duloxetine doses were 40, 60, 80 and 120 mg/day. SSRI doses were 10 mg/day (escitalopram) and 20 mg/day (fluoxetine and paroxetine). Results: Compared to SSRI-treated patients, duloxetine-treated patients had a significantly greater (p ≤ 0.05) reduction in the 17-item Hamilton Depression Rating Scale (HAMD₁₇) total score and HAMD₁₇ items of work and activities, psychomotor retardation, genital symptoms and hypochondriasis. Differences favoring the SSRIs approached significance for middle insomnia (p = 0.057) and late insomnia (p = 0.06), with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine. Similarly, the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms (p = 0.056), with an effect size twice that observed for the SSRIs. The HAMD₁₇total score difference was driven mostly by patients with lower baseline MDD severity (HAMD₁₇ total score ≤19), where the HAMD₁₇ effect size advantage for duloxetine over combined SSRIs was statistically significant (p = 0.031). Conclusion: Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity, and different HAMD₁₇ items responded differently to duloxetine compared with SSRIs. Understanding these differences may be useful in tailoring antidepressant therapy for individual patients.

Combined Paroxetine and Clonazepam Treatment Strategies Compared to Paroxetine Monotherapy for Panic Disorder

Despite the widespread application of combined selective serotonin reuptake inhibitors (SSRI) and benzodiazepine treatment for panic disorder, there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy. Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment, this study is the first to address the critical question of whether continued combined treatment confers superior efficacy. This study is a randomized, double-blind, three-arm study in patients with panic disorder (n = 60), comparing the efficacy and safety of paroxetine and placebo (PP), paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase (PC-D), and ongoing combination treatment (PC-M). All treatment groups demonstrated significant improvement by endpoint. There was a significant advantage for the combined treatment groups early in treatment but, subsequently, outcome in all three groups was similar. A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered. The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout. Combined treatment with paroxetine and clonazepam resulted in more rapid response than with the SSRI alone, but there was no differential benefit beyond the initial few weeks of therapy. Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy.