Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique des Troubles de L’humeur et des Dépendances Comorbides: Une Revue Systématique et une Méta-Analyse

Abstract

Objective: Addiction comorbidity is an important clinical challenge in mood disorders, but the best way of pharmacologically treating people with mood disorders and addictions remains unclear. The aim of this study was to assess the efficacy of pharmacological treatments for mood and addiction symptoms in people with mood disorders and addiction comorbidity. Methods: A systematic search of placebo-controlled randomized controlled trials investigating the effects of pharmacological treatments in people with bipolar disorder (BD) or major depressive disorder (MDD), and comorbid addictions was performed. Treatment-related effects on mood and addiction measures were assessed in a meta-analysis, which also estimated risks of participant dropout and adverse effects. Results: A total of 32 studies met systematic review inclusion criteria. Pharmacological therapy was more effective than placebo for improving manic symptoms (standardized mean difference [SMD] = −0.15; 95% confidence interval [95% CI], −0.29 to −0.02; P = 0.03) but not BD depressive symptoms (SMD = −0.09; 95% CI, −0.22 to 0.03; P = 0.15). Quetiapine significantly improved manic symptoms (SMD = −0.23; 95% CI, −0.39 to −0.06; P = 0.008) but not BD depressive symptoms (SMD = −0.07; 95% CI, −0.23 to 0.10; P = 0.42). Pharmacological therapy was more effective than placebo for improving depressive symptoms in MDD (SMD = −0.16; 95% CI, −0.30 to −0.03; P = 0.02). Imipramine improved MDD depressive symptoms (SMD = −0.58; 95% CI, −1.03 to −0.13; P = 0.01) but Selective serotonin reuptake Inhibitors (SSRI)-based treatments had no effect (SMD = −0.06; 95% CI, −0.30 to 0.17; P = 0.60). Pharmacological treatment improved the odds of alcohol abstinence in MDD but had no effects on opiate abstinence. Conclusions: Pharmacological treatments were significantly better than placebo in improving manic symptoms, MDD depressive symptoms, and alcohol abstinence but were not better for bipolar depression symptoms. Importantly, quetiapine was not more effective than placebo in improving bipolar depression symptoms nor were SSRI’s for the treatment of MDD depression. Our findings highlight the need for further high-quality clinical trials of treatments for mood disorders and comorbid addictions.

Suicide Risk and Addiction: The Impact of Alcohol and Opioid Use Disorders

“…Although not specifically indicated for suicidal ideation or behavior, SSRIs have been used with some success in decreasing suicidal ideation alongside other depressive symptoms, and reducing alcohol misuse in depressed alcohol users [ 101 , 117 – 119 ]. SSRIs consistently produce a modest 15–20% reduction in alcohol consumption [ 120 ], however intra-individual reductions in alcohol intake range widely from 10 to 70% [ 120 ].…”

“…Double-blinded, randomized, placebo-controlled trials for co-occurring MDD/dysthymia and AUD indicate that antidepressants—particularly non-SSRIs—outperform placebo in the treatment of depression [ 122 ], while SSRIs only demonstrate efficacy when restricted to participants without AUD [ 124 ]. Additional meta-analytic research similarly suggests lower performance of SSRIs relative to tricyclics in comorbid MDD and AUD/SUD [ 119 , 125 ], but results should be interpreted cautiously given the potentially mediating roles of study design and sample selection. Additionally, findings regarding depressive symptom reduction are equivocal when controlling for study quality and bias [ 126 ], and antidepressants may not be justified for treatment of alcohol misuse in the absence of MDD [ 118 , 127 ].…”

Which interventions for alcohol use should be included in a universal healthcare benefit package? An umbrella review of targeted interventions to address harmful drinking and dependence.

“…Two studies evaluated pharmacological interventions as a whole. A review of pharmacological treatments for people with concurrent bipolar disorder or depression found no effect on alcohol consumption (SMD − 0.10, 95% CI − 0.24 to 0.04) but did nd an improvement in abstinence (OR 1.46, 95% CI 1.02 to 2.11) [94], unlike a network meta-analysis of pharmacotherapy for AUD which found no improvement in abstinence rate (OR 0.68, 95% CI 0.4 to 1.16, after treatment) [102]. Due to the variation in e cacy across different types of pharmacological intervention, any analysis of pharmacological interventions is likely to be very dependent on the speci c interventions included.…”

“…For topiramate, one low quality network meta-analysis found a signi cant increase in continuous abstinence at 84-365 days (OR 1.88, 95% CI 1.06 to 3.34) [98] and a high quality network meta-analysis found a signi cant reduction in total consumption at 3-52 weeks (SMD − 0.77, 95% CI -1.12 to -0.42; NMD − 0.79, 95% CI -1.21 to -0.36), as well as for drinking days and heavy drinking days, but drinks per drinking day and mortality outcomes were not signi cant, and the study noted very low quality of RCTs alongside presence of publication bias[87]. Certainty in the evidence for anticonvulsants was downgraded to very low, due to high risk of bias, high heterogeneity in RCTs, low precision, and presence of publication bias.Four studies evaluated antidepressants for AUD, of which three considered individuals with comorbid depression [68,74,94]. No signi cant effect was observed on alcohol abstinence among people with comorbid major depressive disorder for nefazodone compared with placebo (OR 2.18, 95% CI 0.68 to 7.07)[94]; AUD remission rate compared to control among individuals with comorbid depression for mirtazapine (SMD − 0.78, 95% CI -1.69 to 0.13)[74], SARI (OR 1.85, 95% CI 0.62 to 5.66)[74], tricyclic antidepressants (OR 1.65, 95% CI 0.57 to 4.73)[74]; or continuous abstinence when compared with placebo at 84-365 days for citalopram or escitalopram (OR 1.03, 95% CI 0.33 to 3.16), nefazodone (OR 0.57, 95% CI 0.19 to 1.76), tianeptine (OR 1.22, 95% CI 0.58 to 2.57), or tiapride (OR 0.56, 95% CI 0.3 to 1.05)[98].…”

Repetitive Transcranial Magnetic Stimulation for Comorbid Major Depressive Disorder and Alcohol Use Disorder

“…Although randomized controlled trials and meta-analyses have shown efficacy for antidepressants in MDD with comorbid AUD [ 7 , 8 ], the effects are modest, with a mix of positive and negative studies [ 8 ], with a recent Cochrane review showing no effect when excluding studies with a high risk of bias [ 7 ]. Similarly, studies for treatments to reduce alcohol use in MDD + AUD remain very limited and without clear effect [ 9 ]. Approved AUD medications, such as naltrexone, have been studied in combination with antidepressants with mixed results [ 10 , 11 , 12 ].…”