To provide an overview of the underlying neurobiology of tobacco smoking in schizophrenia, and implications for treatment of this comorbidity.
Explanations for heavy tobacco smoking in schizophrenia ...include pro-cognitive effects of nicotine, and remediation of the underlying pathophysiology of schizophrenia. Nicotine may ameliorate neurochemical deficits through nicotine acetylcholine receptors (nAChRs) located on the dopamine, glutamate, and GABA neurons. Neurophysiological indices including electroencephalography, electromyography, and smooth pursuit eye movement (SPEM) paradigms may be biomarkers for underlying neuronal imbalances that contribute to the specific risk of tobacco smoking initiation, maintenance, and difficulty quitting within schizophrenia. Moreover, several social factors including socioeconomic factors and permissive smoking culture in mental health facilities, may contribute to the smoking behaviors (initiation, maintenance, and inability to quit smoking) within this disorder.
Tobacco smoking may alleviate specific symptoms associated with schizophrenia. Understanding the neurobiological underpinnings and psychosocial determinants of this comorbidity may better explain these potential beneficial effects, while also providing important insights into effective treatments for smoking cessation.
Abstract
Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect ...putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (
n
= 9) or sham (
n
= 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33,
p
= 0.21; Cohen’s
d
= 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92,
p
= 0.06), and significant reductions in PANSS positive (Estimate = 2.42,
p
= 0.02) and total (Estimate = 5.03,
p
= 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58,
p
< 0.05), and suppressed increased tobacco use that was associated with cannabis reductions (Treatment x Time:
p
= 0.01). Our preliminary findings suggest that rTMS to the DLPFC is safe and potentially efficacious for treating CUD in schizophrenia.
Background
Substance use disorders (SUDs) are a leading cause of disability worldwide. While several pharmacological and behavioral treatments for SUDs are available, these may not be effective for ...all patients. Recent studies using non‐invasive neuromodulation techniques including Repetitive Transcranial Magnetic Stimulation (rTMS), Transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS) have shown promise for SUD treatment.
Objective
Multiple studies were evaluated investigating the therapeutic potential of non‐invasive brain stimulation techniques in treatment of SUDs.
Method
Through literature searches (eg, PubMed, Google Scholar), 60 studies (2000–2017) were identified examining the effect of rTMS, tDCS, or DBS on cravings and consumption of SUDs, including tobacco, alcohol, cannabis, opioids, and stimulants.
Results
rTMS and tDCS demonstrated decreases in drug craving and consumption, while early studies with DBS suggest similar results. Results are most encouraging when stimulation is targeted to the Dorsolateral Prefrontal Cortex (DLPFC).
Conclusions
Short‐term treatment with rTMS and tDCS may have beneficial effects on drug craving and consumption. Future studies should focus on extending therapeutic benefits by increasing stimulation frequency and duration of treatment.
Scientific Significance
The utility of these methods in SUD treatment and prevention are unclear, and warrants further study using randomized, controlled designs. (Am J Addict 2018;27:71–91)
Impulsivity is strongly associated with substance use disorders (SUDs). Our review discusses impulsivity as an underlying vulnerability marker for SUDs, and treatment of co‐occurring impulsivity in ...SUDs. Three factors should be considered for the complex relationship between impulsivity and a SUD: (1) the trait effect of impulsivity, centering on decreased cognitive and response inhibition, (2) the state effect resulting from either acute or chronic substance use on brain structure and function, and (3) the genetic and environmental factors (e.g., age and sex) may influence impulsive behavior associated with SUDs. Both subjective and objective measures are used to assess impulsivity. Together, treatment developments (pharmacological, behavioral, and neurophysiological) should consider these clinically relevant dimensions assessed by a variety of measures, which have implications for treatment matching in individuals with SUD. Despite its heterogeneity, impulsivity is a marker associated with SUDs and may be understood as an imbalance of bottom‐up and top‐down neural systems. Further investigation of these relationships may lead to more effective SUD treatments.
Despite its heterogeneity, impulsivity is a marker associated with substance use disorders (SUDs) and may be understood as an imbalance of bottom‐up and top‐down neural systems. Our review discusses the multifaceted construct of impulsivity as an underlying vulnerability marker within the various stages of SUDs. We emphasize a transdiagnostic model for understanding impulsivity and addiction risk.
: Rates of tobacco smoking are high in people with schizophrenia with greater difficulty of quitting smoking compared to the general population, which also relate to the increased cardiovascular and ...cancer risks in this co-occurring disorder. Therefore, effective smoking cessation pharmacotherapies addressing tobacco co-morbidity are imperative.
: In this review, the authors performed an extensive systematic electronic literature review examining the efficacy and safety of first-line pharmacotherapies for smoking cessation, including varenicline, sustained-release bupropion, and nicotine replacement therapies (NRT) using continuous abstinence rates over 10-12-week periods in smokers with schizophrenia. Twelve trials reporting smoking cessation outcomes using interventions in schizophrenia were included and risk ratio (RR) was used.
: Our findings support the efficacy and safety of first-line pharmacotherapies for the treatment of tobacco use disorder in smokers with schizophrenia. Further research on the long-term effectiveness and safety of these agents in community samples is warranted. Smoking cessation pharmacotherapies may warrant the consideration of the emerging use of electronic nicotine delivery systems while neuromodulation techniques also offer promise.
•This is an overview of the state of tES/TMS applied in drug addictions.•Neuroscience will be translated into tES/TMS tools for clinical practice in addiction.•Heterogeneity of methods and outcome ...measures in the literature are addressed.•This article provides guidelines for best practices in tES/TMS addiction research.
There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.
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