GME Research Review is a monthly newsletter where internationally recognized experts select, summarize, and provide a clinical commentary on the latest published research in psychiatry. Each summary has been derived from the relevant article’s abstract and the clinical commentary has been provided by our expert.
Cahill K, Steven S, Perera R, Lancaster T.
Cochrane Database Syst Rev. 2013 May 31;5:CD009329.
Objectives: There were 4 objectives of this overview and comparative effectiveness of various firs- line pharmacotherapies for smoking cessation.
Tobacco use kills almost half a million Americans annually, making it the most deadly addictive disorder. However, it is very treatable as demonstrated in the review of reviews. For every two smokers a psychiatrist helps quit, one life will be saved from premature mortality. Medications roughly double the chances of success for every quit attempt. Of note, the findings are so robust for nicotine replacement therapy (NRT), additional studies to establish efficacy are not needed. What is needed is for clinicians to use these evidence-based therapies, and this review confirms the evidence that prescribers have safe and effective options for all patients. Tobacco use disorders are highly prevalent in patients with other addictions and mental illness. Although relapse is common, repeated or even extended treatment may be necessary. In patients with psychiatric comorbidity, the choice of medication might pose a concern. However, at least two medications have indications for other psychiatric conditions, namely bupropion and nortriptyline, that are also effective options in patients who smoke. Varenicline might be associated with idiosyncratic neuropsychiatric side effects so education and monitoring is required for emergent depression and suicidal or homicidal ideation. From a safety perspective, NRT does not provide the 4000-7000 chemicals present in smoke that are associated with harm. Combination NRT maybe more effective because a greater percent of baseline nicotine is replaced. The reviews included in this study also establish that concurrent smoking with NRT is safe and more effective than quitting abruptly. Although not specifically included in this review, there is evidence of safety for the use of varenicline in patients with stable schizophrenia. This review also did not address the role of nicotine to manage acute nicotine withdrawal in psychiatric patients admitted to hospitals where they are not allowed to smoke. In conclusion, psychiatrists can be reassured that they can treat patients who smoke with a combination of pharmacotherapy and counseling to reduce the premature mortality that frequently befalls these patients.
Levin FR, Mariani J, Brooks DJ, et al
Objectives: Is venlafaxine-extended release (VEN-XR) an effective treatment for cannabis dependence with concurrent depressive disorders?
The primary outcome measures were: (1) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and; (2) improvement in depressive symptoms based on the HRDS. Missing data was interpreted as being positive for use of marijuana.
Conclusions: Contrary to what the authors expected, for depressed, cannabis-dependent patients, venlafaxine XR does not appear to be effective at reducing depression and may lead to an increase in cannabis use. Also heavily dependent users had a worse prognosis in this study.
Cannabis is the most widely used illicit substance worldwide, with significant consequences including an increased risk of psychosis in vulnerable individuals. Cannabis dependence doubles the odds of a depressive disorder in the general population and depression is very common in cannabis dependence treatment-seeking patients. The investigators chose to study venlafaxine because of its dual action on serotonin and noradrenergic systems. This was justified on the basis of previous RCTs where tricyclic antidepressants appeared to be superior to selective serotonin reuptake inhibitors in reducing substance use in depressed patients. The patients recruited were a mix of clinical treatment seekers and those recruited via advertisement. They used the SCID to define the population and excluded those whose mood symptoms could be attributed to cannabis withdrawal. Of the subjects, 62% completed all 12 weeks of the trial. This negative trial demonstrates a significant difference between placebo and venlafaxine in this population and it could be argued that the medication increases cannabis use. The lack of effect of the active medication could be due to the ceiling effect of response produced by cognitive-behavioral therapy (CBT). Most subjects had mild to moderate depression, which is very responsive to CBT without any additional benefit from medication. The increase in use of cannabis could be explained by the adrenergic effects of venlafaxine worsening cannabis withdrawal. However, this is speculative at best. For every one patient who would achieve abstinence with CBT and placebo, four would be harmed by the addition of venlafaxine XR. In conclusion, in depressed outpatients using cannabis, it might be prudent to engage the patient in CBT to stop or reduce marijuana use before initiating treatment for depression, and venlafaxine is best avoided. However, practical considerations such as patients perceptions of the antidepressant and anxiolytic effects of marijuana will require psychoeducation and motivational interviewing to engage in CBT.
Goodwin RD, Stein DJ.
Psychiatry Clin Neurosci. 2013;67(3):167-173.
Conclusions: The strongest association was between panic disorder and past substance dependence. The authors suggest this might be due to the effects of substances on the neurocircuitry involved in panic, such as the extended amygdala. Moreover, there was an association between anxiety disorders and substance dependence not accounted for by depression or alcohol dependence. The limitations include the cross sectional nature of the study; thus, no inferences can be drawn on causality. The specificity as to which substance caused the problem was not possible due to limited sample sizes in the cells.
In this study, substance dependence predated the onset of anxiety disorders, suggesting that self-medication might not always be the reason patients use drugs. This study points to the possibility of a substance-induced anxiety disorder or some shared vulnerability to both. Substance use is a stigmatized behavior and may be underreported in traditional psychiatric and primary care settings whilst treating anxiety disorders. Anxiety disorders are common reasons to seek care, and the use of benzodiazepines to manage these symptoms in the short term might cause vulnerable individuals to develop or worsen substance dependence. Regardless, clinicians need to be able to prevent harm and yet offer treatment to those who present with impairing levels of anxiety. Therefore, it is imperative to screen for lifetime and current substance use prior to the initiation of benzodiazepines. Moreover, stimulant use disorders and marijuana use might also be the cause of anxiety and these substance-induced anxiety disorders need to be ruled out or treated with appropriate addiction counseling before the initiation of benzodiazepines. Screening tests can include obtaining a detailed history with third-party corroboration where feasible, and a urine toxicology screen. Moreover, newer screening tools such as the Global Assessment of Individual Need-Short Screener (GAIN-SS) are highly valid and reliable whilst being easy to administer in busy ambulatory settings. There is little evidence published on the management of co-occurring anxiety disorders in patients with substance use disorders. Therefore, to balance the need for symptom control and to prevent or worsen the course of a substance use disorder, it is important to use non-addictive alternatives such as SSRIs combined with CBT to treat the anxiety disorder. Concurrent treatment of the addiction is also warranted. If benzodiazepines are prescribed, those with lower abuse liability such as clonazepam should be used. Short duration of prescriptions with pill counts and monitoring of urine toxicology might optimize management and reduce the risk of iatrogenic addiction. A pragmatic goal of treatment in patients with concurrent addiction and anxiety disorders might be improvement in quality of life and fulfillment of role responsibilities rather than complete abstinence from benzodiazepines. Further research is required to determine the optimal management of these patients.
Krupitsky E, Zvartau E, Blokhina E, et al
Arch Gen Psychiatry. 2012;69(9):973-981.
(1) Naltrexone implant 1000 mg and oral placebo (NI+OP group; 102 patients)
(2) Placebo implant and 50-mg oral naltrexone HCL (PI+ON group; 102 patients)
(3) Placebo implant and oral placebo (PI+OP group; 102 patients).
Conclusions: In regions where there is no access to opioid agonist therapy, injectable naltrexone was found to be superior to oral naltrexone in retaining patients in treatment for up to 6 months. About half the patients responded to treatment and half of these relapsed after treatment ends, indicating the need for chronic treatment.
The standard of care for opioid dependence in North America is agonist therapy with methadone or buprenorphine. However, there are patients for whom these medications are not an option either due to personal choice or availability of treatment. Injectable naltrexone, which is available in the US, might be an alternative for these patients and negates the need for daily observed ingestion of the oral formulation. Although the oral formulation performed better than placebo, these subjects had engaged family members who supervised their medication compliance. There were no reports of depression, anxiety, or anhedonia, suggesting the implant was well tolerated. The limitations of the implant are the invasive nature of the procedure and failure in 13% of subjects. Cravings were also reduced in those who remained abstinent. Given the high prevalence of HIV in this population, any treatment that can reduce injection potentially reduces the spread of the disease to others. Therefore, this option deserves serious consideration for the appropriate opioid-dependent patient who does not or cannot tolerate an opioid agonist. Weighing the risks and benefits, including the lack of efficacy of opioid agonists for acute pain should the patient require pain management, will help the patient and provider decide if this approach is a viable option. It should be noted that the implant is not available in the US but a sustained-release injectable formulation is available and is administered every 30 days. Moreover, naltrexone injection is also approved for alcohol dependence and might be well suited for those with dual opioid and alcohol dependence. In summary, naltrexone can be effective if the problem of non-adherence can be overcome by injecting or implanting a sustained-release formulation of the medication.
Boschloo L, Vogelzangs N, van den Brink W, et al
To identify independent risk factors of the recurrence of alcohol dependence (AD) in people with a remitted disorder at baseline and persistence of AD in people with a current disorder at baseline.
Conclusions: Both recurrence and persistence of alcohol dependence are highly dependent on severity of baseline alcohol problems, whereas severity of depressive/anxiety symptoms predicts only the recurrence of alcohol dependence. Both measures may be useful in identifying people at an increased risk of a negative course and who could be targeted by prevention strategies.
Only 2 to 6% of treated patients with alcohol dependence remit annually. The strength of this cohort study is that participants were heterogeneous and selected from community settings, primary care settings, and mental health settings with follow-up rates of >80%. The findings suggest that therapeutic nihilism is not warranted because the majority of subjects remit within 2 years and it is not always a chronic and relapsing disorder. The severity of alcohol problems and depressive/anxiety symptoms may be useful in identifying people at an increased risk of developing a new episode of AD. Assessment instruments such as the AUDIT , IDS, and BAI may be used to screen for alcohol problems, depressive symptoms, or anxiety symptoms, respectively. Given that the recurrence rate was only 2% in the quintile of people with the mildest alcohol problems versus 43% in the quintile of people with the most severe alcohol problems, these findings might be useful to personalize advice regarding additional treatment. The observation might be explained by either a shared diathesis for both depression/anxiety symptoms and alcohol dependence or “self-medication,” where the person is trying to mitigate negative mood states by drinking alcohol. Alcohol use disorders present a particular challenge for psychiatrists. Although alcohol use is associated with all psychiatric disorders, the causal link between the two is less well established. Often the clinician is not sure if the patient is self-medicating symptoms of anxiety or depression or if the depression or anxiety is due to alcohol intake. Although the temporal association between use and affective symptoms might provide a clue, the ideal intervention would be to examine the effects of alcohol withdrawal treatment on affective symptoms and treat residual symptoms of depression or anxiety with SSRIs and CBT. Most alcohol-induced mood disorders improve dramatically within 1-2 weeks of abstinence. In addition, it is important to assess the immediacy of risk to the patient since most completed suicides occur during intoxication. Such patients need admission, detoxification, relapse-prevention medication such as naltrexone or acamprosate, the appropriate SSRI, and CBT and addiction counseling. Ideally, this should be provided concurrently wherever possible or at least collaboratively by mental health and addiction treatment providers. Therapy should initially focus on maintaining sobriety and resolving the effects of past trauma where appropriate, and management of depression and or anxiety with medications with low abuse potential. Monitoring the effects of SSRIs on drinking is also warranted given that some studies have found increased rates of drinking. Long-term benzodiazepine prescriptions should be avoided given the greater risk of dependence in patients with AD.
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