Article

Ninety-three cases of alcohol dependence following SSRI treatment

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Abstract

Background: There have been recent reports linking serotonin reuptake inhibitor use with increased alcohol consumption. A syndrome of alcoholism precipitated by a common treatment has clear implications for both research and treatment if it is a common phenomenon. Objective: To explore the profile of people affected, and drugs that might trigger the syndrome. Methods: We have selected reports to RxISK.org reporting the problem and cases linked to a blog posting outlining the syndrome and mined these for data on age, gender, drug of use, pattern of outcome on treatment, and impact of the problem. Results: The data make it clear that all treatments with significant effects on the serotonin reuptake system are likely to cause this problem. Both sexes, and all ages are affected and reports have come from a range of countries. While stopping treatment can lead to the problem clearing, a failure to stop can result in death. Conclusions: SSRI induced alcoholism is likely to be a relatively common problem. Recognizing the problem can lead to a gratifying cure. A failure to recognize it can be fatal.

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... Although initial studies suggest that Selective Serotonin Reuptake Inhibitors (SSRIs), the most commonly used class of antidepressants, reduce alcohol consumption in heavy drinkers by 15-20% ( Naranjo and Bremner 1993 ), subsequent placebo controlled trials have not found a reduction in alcohol drinking ( Kranzler et al., 1995 ). Moreover, several studies suggest a possible negative role of antidepressant treatment on alcohol consumption since some depressed patients show an enhanced craving for alcohol or develop alcohol-dependence after using these drugs ( Atigari et al., 2013;Brookwell et al., 2014;Charney et al., 2015;Menkes and Herxheimer 2014 ). ...
... Other alterations in the en-docannabinoid system that were found in both the fluoxetine and the bupropion-treated groups are also compatible with a neuroprotective response of the brain by the endocannabinoid and N -acylethanolamine systems (see Pistis and Muntoni 2017;Sanchez-Marin et al. 2017 ). However, the observed alterations in gene expression of Cnr2 and Ppar α, which were observed only in the fluoxetine-treated group, suggest a greater extent of cannabinoid disruption in this group, and this could be related to the increased alcohol consumption during relapse observed in this group (see Anderson 2018;Atigari et al., 2013;Brookwell et al., 2014;Charney et al., 2015;Menkes and Herxheimer 2014 ). ...
... All these data are coherent with the presence of alterations in neuroplasticity in those animals that showed an enhanced relapse to alcohol drinking after the fluoxetine treatment, similar to those present in inflammatory processes and that have also been reported for mood disorders and in the establishment of addiction ( Leclercq et al., 2017 ). Alterations in brain functions similar to those observed in our study could be involved in the numerous clinical cases and reports that describe negative effects of antidepressants on alcohol consumption and/or depression (see Atigari et al., 2013;Brookwell et al., 2014;Charney et al., 2015;Menkes and Herxheimer 2014 ). ...
Article
Rationale: the role that antidepressants play on alcohol consumption is not well understood. Previous studies have reported that treatment with a Selective Serotonin Reuptake Inhibitor (SSRIs) increases alcohol consumption in an animal model of relapse, however it is unknown whether this effect holds for other antidepressants such as the atypical dopamine/norepinephrine reuptake inhibitors (SNDRI). Objectives: the main goal of the present study was to compare the effects of two classes of antidepressants drugs, bupropion (SNDRI) and fluoxetine (SSRI), on alcohol consumption during relapse. Since glutamatergic and endocannabinoid signaling systems plays an important role in alcohol abuse and relapse, we also evaluated the effects of both antidepressants onthe expression of the main important genes and proteins of both systems in the prefrontal cortex, a critical brain region in alcohol relapse. Methods: rats were trained to self-administered alcohol. During abstinence, rats received a 14d-treatment with vehicle, fluoxetine (10 mg/kg) or bupropion (20 mg/kg), and we evaluated alcohol consumption during relapse for 3 weeks. Samples of prefrontal cortex were taken to evaluate the mRNA and protein expression of the different components of glutamatergic and endocannabinoid signaling systems. Results: fluoxetine treatment induced a long-lasting increase in alcohol consumption during relapse, an effect that was not observed in the case of bupropion treatment. The observed increases in alcohol consumption were accompanied by distinct alterations in the glutamate and endocannabinoid systems. Conclusions: our results suggest that SSRIs can negatively impact alcohol consumption in relapse while SNDRIs have no effects. The observed increase in alcohol consumption are accompanied by functional alterations in the glutamatergic and endocannabinoid systems. This finding could open new strategies for the treatment of depression in patients with alcohol use disorders.
... Additionally, a recent study reported 93 cases in which SSRI treatment was associated with increased cravings and alcohol consumption (Brookwell et al., 2014). Pretreatment alcohol consumption ranged from minimal drinking to alcohol dependence. ...
... Pretreatment alcohol consumption ranged from minimal drinking to alcohol dependence. Regardless of pattern of alcohol consumption prior to treatment, over 70% of cases showed an increase in consumption and cravings during SSRI treatment that reverted to the original drinking pattern upon cessation of SSRI administration (Brookwell et al., 2014). It is important to note that these were subjective reports, and a causal link between SSRI treatment and increased alcohol consumption cannot be confirmed. ...
... Moreover, AP-2β-enhanced serotonergic transmission may also contribute to alcohol abuse, perhaps through inhibition of 5-HTT [19,20,101] and lowering MAO [28,[91][92][93]. In agreement with this notion, increased serotonin levels or 5-HTT KO mice have been found to trigger alcoholism [158][159][160], and MAO-A methylation is associated with alcoholism in women [161]. Furthermore, alcoholics have higher levels of both, the transcript and protein of tryptophan hydroxylase, TPH [162], the rateliming enzyme in serotonin synthesis, which has a binding site for AP-2β in its promotor [107]. ...
Article
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Monoaminergic neurotransmitter systems play a central role in neuronal function and behaviour. Dysregulation of these systems gives rise to neuropsychiatric and neurodegenerative disorders with high prevalence and societal burden, collectively termed monoamine neurotransmitter disorders (MNDs). Despite extensive research, the transcriptional regulation of monoaminergic neurotransmitter systems is not fully explored. Interestingly, certain drugs that act on these systems have been shown to modulate central levels of the transcription factor AP-2 beta (AP-2β, gene: TFAP2Β). AP-2β regulates multiple key genes within these systems and thereby its levels correlate with monoamine neurotransmitters measures; yet, its signalling pathways are not well understood. Moreover, although dysregulation of TFAP2Β has been associated with MNDs, the underlying mechanisms for these associations remain elusive. In this context, this review addresses AP-2β, considering its basic structural aspects, regulation and signalling pathways in the controlling of monoaminergic neurotransmitter systems, and possible mechanisms underpinning associated MNDS. It also underscores the significance of AP-2β as a potential diagnostic biomarker and its potential and limitations as a therapeutic target for specific MNDs as well as possible pharmaceutical interventions for targeting it. In essence, this review emphasizes the role of AP-2β as a key regulator of the monoaminergic neurotransmitter systems and its importance for understanding the pathogenesis and improving the management of MNDs.
... The use of selective serotonin reuptake inhibitors (SSRI) is controversial, since they could trigger heavy drinking, especially for type B alcoholism (earlier onset, more alcohol intake) (30). Furthermore, a series of 93 cases describes even the onset of alcohol dependence after therapy with SSRIs for MDD (31). Still, a safer alternative could be naltrexone in combination with sertraline (but not escitalopram), with positive effects on this dual diagnosis (32). ...
Article
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Introduction: Dual diagnosis is frequent among psychiatric patients. Alcohol use disorder (AUD) negatively affects the treatment and the progression of co-occurring disorders. The reverse could also be valid, other symptoms of other diseases and therapies may hinder the achievement and maintenance of abstinence. Aim: The aim of the present study is to assess the frequency of psychiatric and medical comorbidities, of the prescribed drugs and the hospital costs related to AUD. Methods: Using AtlasMed database, we searched the patients admitted to the Cluj County Emergency Hospital st Psychiatry Department between January the 1 and st December 31 2016, with a main or secondary diagnosis of alcohol dependence. The socio-demographic (age, gender, geographic area), the psychiatric and medical diagnosis and the prescribed psychotropic medications were recorded. Results: 623 alcoholic patients were admitted to the Cluj County Emergency Hospital Psychiatry Department, during a one year span, mostly men, accounting for 23% of the total number of hospitalisations and 12.1% of the hospital costs. The most frequent psychiatric comorbidities were personality disorders, major depressive disorder (MDD), neurocognitive disorders, alcohol-related psychosis and suicide attempts. The most common medical conditions in alcoholics were alcoholic liver disease (ALD), cardiovascular disease, dyslipidemia, alcoholic polyneuropathy, alcoholic pancreatitis, type 2 diabetes and head injuries. The most commonly prescribed psychiatric medications were benzodiazepines, anticonvulsants and tiapride. Conclusions: Alcohol dependence has become an increasingly stringent public health problem, from the point of view of prevalence, frequent admittances, relapses and comorbidities.
... In addition to the mentioned low overall effectiveness, it is important to mention that some studies reported even poorer drinking outcomes in AUD patients treated with SSRIs compared to those treated with placebo [100][101][102]. In this line, studies have reported clinical cases where treatment with SSRIs appears to be the cause of increased frequency of intoxication by alcohol and new onset of alcohol-related problems [103][104][105]. Finally, patients who actively drink suffering of comorbid anxiety and AUD have also shown that they may increase alcohol consumption under treatment with SSRIs [106]. ...
... Although some antidepressants are prescribed for treatment of nicotine cessation such as bupropion and nortriptyline [82], antidepressants have generally shown little efficacy for the treatment of cocaine addiction [83] or the abuse of other substances, such as alcohol or opioids [84]. There is also evidence that SSRIs might increase alcohol intake [85]. These results may seem contrary since drugs of abuse with higher selectivity for serotonin transporters are less reinforcing than those more selective for dopamine. ...
Article
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Purpose of Review This review considers the contribution of monoamine neurotransmitters to anhedonia, substance abuse, and sexual dysfunction and the relationship between antidepressant efficacy and abuse liability. Recent Findings The use of drugs with known abuse potential to treat depression, the addition of psychostimulants with antidepressants, and the development of novel antidepressants with preclinical evidence for abuse liability have increased in recent years. This is in contrast to the general lack of abuse potential reported for traditional antidepressants such as selective serotonin reuptake inhibitors. While these new strategies might have the benefit of reduced sexual dysfunction, it is at the expense of increased abuse liability. Summary Increasing extracellular dopamine may both increase antidepressant efficacy and reduce sexual dysfunction, but it increases abuse potential. Preclinical researchers should incorporate behavioral economics to assess both antidepressant efficacy and abuse liability while clinicians need to be aware of this relationship in considering novel treatments.
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Children's mental health services are said to be the biggest failure in Britain's National Health Service, specially, with regard to the treatment of depression and suicidal behaviour in children and adolescents. The use of antidepressants in children and adolescents shows the largest gap existing in health services between clinical practice and scientific evidence, among open label studies that claim its benefits and a big number of randomized controlled trials (RCTs) that indicate the opposite, and among RCTs as they are published and advertised and what their data actually prove. However, antidepressants are commonly used and they probably are the most prescribed drugs in adolescents. The context of antidepressant use during childhood, the evidence analysis, the harms and risks, the increase of suicidal events, and other issues related to clinical practice are addressed. The place of SSRIs in clinical practice might be related to their potential serenic effect, different from the anxiolytic effect of benzodiazepines and antipsychotics. If “this therapeutic principle” were considered as primary outcome, it would allow a better understanding of RCT data and a clinical practice based on a more balanced risk-benefit ratio. Its application would require a collaborative work with patients and a significant degree of autonomy with regards to what is included in the clinical guidelines. The paper examines general troubles of healthcare services, their sustainability, health promotion, and drug use, comparing the diagnosis and treatment of child and youth depression with those of osteoporosis and other diseases, like asthma and high blood pressure. Finally, a free access campaign to clinical trial data is advocated.
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Background: Anxiety disorders are a potentially disabling group of disorders that frequently co-occur with alcohol use disorders. Comorbid anxiety and alcohol use disorders are associated with poorer outcomes, and are difficult to treat with standard psychosocial interventions. In addition, improved understanding of the biological basis of the conditions has contributed to a growing interest in the use of medications for the treatment of people with both diagnoses. Objectives: To assess the effects of pharmacotherapy for treating anxiety in people with comorbid alcohol use disorders, specifically: to provide an estimate of the overall effects of medication in improving treatment response and reducing symptom severity in the treatment of anxiety disorders in people with comorbid alcohol use disorders; to determine whether specific medications are more effective and tolerable than other medications in the treatment of particular anxiety disorders; and to identify which factors (clinical, methodological) predict response to pharmacotherapy for anxiety disorders. Search methods: Review authors searched the specialized registers of The Cochrane Collaboration Depression, Anxiety and Neurosis Review Group (CCDANCTR, to January 2014) and the Cochrane Drugs and Alcohol Group (CDAG, to March 2013) for eligible trials. These registers contain reports of relevant randomized controlled trials (RCT) from: the Cochrane Central Register of Controlled Trials (CENTRAL, all years), MEDLINE (1950 to date), EMBASE (1974 to date) and PsycINFO (1967 to date). Review authors ran complementary searches on EMBASE, PubMed, PsycINFO and the Alcohol and Alcohol Problems Science Database (ETOH) (to August 2013). We located unpublished trials through the National Institutes of Health (NIH) RePORTER service and the World Health Organization (WHO) International Clinical Trials Registry Platform (to August 2013). We screened reference lists of retrieved articles for additional studies. Selection criteria: All true RCTs of pharmacotherapy for treating anxiety disorders with comorbid alcohol use disorders. Trials assessing drugs administered for the treatment of drinking behaviour, such as naltrexone, disulfiram and acomprosate were not eligible for inclusion in this systematic review. 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We regarded one trial as being at high risk of bias due to selective reporting.Study participants had Diagnostic and Statistical Manual (DSM) III- and DSM IV-diagnosed alcohol use disorders and post-traumatic stress disorder (two studies), social anxiety disorder (SAD; two studies) or generalized anxiety disorder (GAD; one study). Four trials assessed the efficacy of the selective serotonin re-uptake inhibitors (SSRIs: sertraline, paroxetine); one RCT investigated the efficacy of buspirone, a 5-hydroxytryptamine (5-HT) partial agonist. Treatment duration lasted between eight and 24 weeks. Overall, 70% of participants included in the review were male.There was very low quality evidence for an effect of paroxetine on global clinical response to treatment, as assessed by the Clinical Global Impressions - Improvement scale (CGI-I). 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Major depression and alcohol problems are common in primary care, yet little is known about the prevalence of alcohol problems in patients with depression or alcohol's effect on depression outcomes. We strove to answer the following questions: How common are alcohol problems in patients with depression? Does alcohol affect the course of depression, response to antidepressant therapy, risk of suicide/death, social functioning and health care utilization? In which alcohol categories and treatment settings have patients with depression and alcohol problems been evaluated? English language studies from MEDLINE, PsychINFO, and Cochrane Controlled Trial Registry were reviewed. Studies were selected using predefined criteria if they reported on the prevalence or effects of alcohol problems in depression. Thirty-five studies met criteria and revealed a median prevalence of current or lifetime alcohol problems in depression of 16% (range 5-67%) and 30% (range 10-60%), respectively. This compares with 7% for current and 16-24% for lifetime alcohol problems in the general population. There is evidence that antidepressants improve depression outcomes in persons with alcohol dependence. Alcohol problems are associated with worse outcomes with respect to depression course, suicide/death risk, social functioning, and health care utilization. The majority of the studies, 34 of 35 (97%), evaluated alcohol abuse and dependence, and 25 of 35 (71%) were conducted in psychiatric inpatients. We conclude that alcohol problems are more common in depression than in the general population, are associated with adverse clinical and health care utilization outcomes, and that antidepressants can be effective in the presence of alcohol dependence. In addition, the literature focuses almost exclusively on patients with alcohol abuse or dependence in psychiatric inpatient settings, and excludes patients with less severe alcohol problems and primary care outpatient settings.
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One hundred and eleven male patients with alcohol dependence and 123 nonalcoholic healthy men were tested for the genetic polymorphisms of alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2 (ALDH2), serotonin transporter (5-HTT) and dopamine transporter (DAT1). There were significant differences in genotype frequencies of ADH2 C992G and A13543G SNPs between alcoholic patients with family history of alcohol dependence (familial) and alcoholic patients without family history (non-familial). Genotype and allele frequencies of ALDH2 G1951A SNP in familial or non-familial alcoholic patients differ from normal controls. Neither 5-HTTLPR L/S nor DAT1 G2319A SNP genotypes nor alleles discriminated alcoholic patients from normal controls. These findings suggest that the genetic characteristics of alcohol metabolism in non-familial alcoholics fall between non-alcoholism and familial alcoholics.