Medication-Induced Weight Change Across Common Antidepressant Treatments : A Target Trial Emulation Study.

BACKGROUND: Antidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited. OBJECTIVE: To compare weight change across common first-line antidepressant treatments by emulating a target trial. DESIGN: Observational cohort study over 24 months. SETTING: Electronic health record (EHR) data from 2010 to 2019 across 8 U.S. health systems. PARTICIPANTS: 183 118 patients. MEASUREMENTS: Prescription data determined initiation of treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The investigators estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months after initiation. Inverse probability weighting of repeated outcome marginal structural models was used to account for baseline confounding and informative outcome measurement. In secondary analyses, the effects of initiating and adhering to each treatment protocol were estimated. RESULTS: Compared with that for sertraline, estimated 6-month weight gain was higher for escitalopram (difference, 0.41 kg [95% CI, 0.31 to 0.52 kg]), paroxetine (difference, 0.37 kg [CI, 0.20 to 0.54 kg]), duloxetine (difference, 0.34 kg [CI, 0.22 to 0.44 kg]), venlafaxine (difference, 0.17 kg [CI, 0.03 to 0.31 kg]), and citalopram (difference, 0.12 kg [CI, 0.02 to 0.23 kg]); similar for fluoxetine (difference, -0.07 kg [CI, -0.19 to 0.04 kg]); and lower for bupropion (difference, -0.22 kg [CI, -0.33 to -0.12 kg]). Escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight, whereas bupropion was associated with 15% reduced risk. When the effects of initiation and adherence were estimated, associations were stronger but had wider CIs. Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion). LIMITATION: No data on medication dispensing, low medication adherence, incomplete data on adherence, and incomplete data on weight measures across time points. CONCLUSION: Small differences in mean weight change were found between 8 first-line antidepressants, with bupropion consistently showing the least weight gain, although adherence to medications over follow-up was low. Clinicians could consider potential weight gain when initiating antidepressant treatment. PRIMARY FUNDING SOURCE: National Institutes of Health.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study.

Background: Treatment of neuropathic pain is challenging. Pregabalin and duloxetine are used as first-line therapy. Various international guidelines recommend a combination of first-line agents for the management of neuropathic pain. The objective of this study was to evaluate the efficacy and safety of a fixed-dose combination (FDC) of low-dose pregabalin and duloxetine compared to pregabalin monotherapy at week 7 in patients with moderate to severe neuropathic pain. Methods: This was a phase 3, randomized, double-blind, double-dummy parallel-group non-inferiority study conducted at 17 sites across India. Three hundred and twenty-eight adult patients with moderate to severe neuropathic pain were randomized in a ratio of 1:1 to receive a FDC of pregabalin and duloxetine or pregabalin monotherapy for 7 weeks followed by a one-week follow-up. The pregabalin-duloxetine combination was initiated at 50 plus 20 mg per day and gradually titrated to a maximum of 75mg plus 30mg twice daily. Pregabalin was initiated at 75mg/day and gradually titrated to a maximum of 150mg twice daily. The main efficacy outcome was a mean change in pain intensity at the end of 7 weeks. Results: Two hundred and ninety-eight patients completed the study, 148 in the pregabalin-duloxetine group and 150 in the pregabalin group. The mean change in daily pain at 7 weeks was as follows: -4.49 with FDC and -4.66 with pregabalin (p<0.0001). The non-inferiority of a low-dose FDC compared to pregabalin monotherapy was demonstrated at the end of the study. The incidence of dizziness and somnolence was comparable between both treatments. A higher frequency of peripheral oedema was observed with pregabalin monotherapy than in the FDC group (p>0.05). Conclusions: A FDC of low doses of pregabalin and duloxetine and high dose of pregabalin monotherapy achieved similar analgesia with dizziness, and somnolence as the most frequent adverse event. Trial registration: CTRI/2020/09/027555.

Spontaneous Ejaculation Due to Duloxetine: A Case Report

ABSTRACT Ejaculation is controlled by both the sympathetic and parasympathetic system and consists of an emission and expulsion phase. Ejaculation latency time is regulated by the sympathetic system. Hypothetically, by reducing ejaculatory latency time, spontaneous ejaculation can occur. Extending the duration of ejaculation is a well-known side effect of antidepressants, especially selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors and noradrenergic reuptake inhibitors. Adrenergic drugs are sometimes used as treatment for delayed ejaculation. A spontaneous ejaculation due to the use of these drugs has rarely been reported. Although most reports of spontaneous ejaculations are related to the use of venlafaxine and reboxetine, this study is based on a case of the side effect of duloxetine.

La depresión: un desafío en la práctica médica general / La depresión: un desafío en la práctica médica general

Asociada o no a una enfermedad orgánica, la depresión tiene gran prevalencia en la práctica médica pero es subdiagnosticada. El trastorno del ánimo suele coexistir con variadas quejas somáticas y dolores crónicos, configurando síndromes mixtos con un diagnóstico diferencial complejo. En este artículo se describen distintas presentaciones clínicas de la depresión en medicina general, con énfasis en los estados depresivos atípicos, depresiones enmascaradas muy relevantes por su frecuencia y consecuencias: depresión posquirúrgica, cuadros dolorosos crónicos como cefaleas o lumbago, la fatiga crónica y la fibromialgia. Solo el reconocimiento y diagnóstico de la depresión subyacente posibilitará la implementación de las adecuadas intervenciones terapéuticas. Se revisan también algunas recomendaciones para el uso de antidepresivos en atención primaria y la eventual consulta psiquiátrica. (AU)

Associated or not with an organic disease, depression has a high prevalence in medical practice but is underdiagnosed. The mood disorder usually coexists with varied somatic complaints and chronic pain, forming mixed syndromes with a complex differential diagnosis. This article describes different clinical presentations of depression in general medicine, with emphasis on atypical depressive states, masked depressions very relevant for their frequency and consequences: post-surgical depression, chronic painful conditions such as headaches or lumbago, chronic fatigue and fibromyalgia. Only the recognition and diagnosis of the underlying depression will enable the implementation of appropriate therapeutic interventions. Some recommendations for the use of antidepressant drugs in primary care and the eventual psychiatric consultation are also reviewed. (AU)