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Treatment of co-occurring anxiety disorders and substance use disorders

co-occurring anxiety disorders and substance use disorders Official reprint from UpToDate www.uptodate.com ©2013

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Treatment of co-occurring anxiety disorders and substance

Treatment of co-occurring anxiety disorders and substance use disorders

Authors Sudie Back, PhD Megan M Moran-Santa Maria, PhD

Disclosures

Section Editor Murray B Stein, MD, MPH

Deputy Editor Richard Hermann, MD

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2013. | This topic last updated: Dez 14, 2012.

INTRODUCTION Anxiety disorders and substance use disorders (SUDs) commonly co-occur [1-3]. The association between these disorders is multifaceted. Anxiety disorders may increase the risk for the development of SUDs, and may alter the presentation and treatment outcome of SUDs. SUDs may alter the presentation and outcome of treatment for anxiety disorders.

The complexity of these comorbidities highlights the importance of a comprehensive understanding of symptoms of each disorder, proper diagnosis, and use of effective treatments, as well as consideration of potentially toxic drug-drug interactions, medication abuse liability, and patient adherence.

This topic reviews treatment of co-occurring anxiety disorders and SUDs. The epidemiology, pathogenesis, clinical manifestations, course, and diagnosis of co-occurring anxiety disorders and SUDs are described separately. Treatment of individual, noncomorbid anxiety disorders are described separately. Treatment of individual, noncomorbid SUDs are described separately. (See "Pharmacotherapy for obsessive-compulsive disorder" and "Psychotherapy for obsessive-compulsive disorder" and "Pharmacotherapy for panic disorder" and "Psychotherapy for panic disorder" and "Pharmacotherapy for generalized anxiety disorder" and "Pharmacotherapy for social anxiety disorder" and "Pharmacotherapy for posttraumatic stress disorder" and "Psychotherapy for posttraumatic stress disorder" and "Treatment of opioid abuse and dependence" and "Cannabis use disorder: Treatment, prognosis, and long-term medical effects" and "Pharmacotherapy for alcohol use disorder" and "Psychosocial treatment of alcohol use disorder" and "Brief intervention for unhealthy alcohol and other drug use" and "Cocaine use disorder in adults: Epidemiology, pharmacology, clinical manifestations, medical consequences, and diagnosis".)

OVERVIEW Clinical trials have identified medications and psychotherapies that effectively treat individual, noncomorbid anxiety disorders as well as individual, noncomorbid substance use disorders (SUDs). However, evidence from clinical trials, described below, is generally inadequate to determine the effectiveness of these interventions in treating co-occurring anxiety disorders and SUDs.

Treating the SUD without addressing the anxiety disorder may render the patient vulnerable to relapse in the face of anxiety symptoms. Treating the anxiety disorder without addressing and monitoring the SUD will likely result in ineffective treatment. Anxiety symptoms may undermine treatment outcome by serving as a trigger for relapse. SUD patients need to learn skills for managing and/or accepting anxiety symptoms without using substances. As an example, patients with panic disorder who complete exposure or other anxiety-provoking homework assignments while under the influence of alcohol or drugs will not experience the rise and fall of anxiety during those assignments, nor will they learn that they are able to withstand the anxiety without using alcohol or drugs.

APPROACH TO TREATMENT Integrated cognitive-behavioral therapy (CBT) has been developed to treat both anxiety disorders and substance use disorders (SUDs) when the two disorders co-occur [4]. Integrative CBT is comprised of cognitive and behavioral interventions that have been found to be effective for noncomorbid anxiety disorders and SUDs individually. The therapy can be used for co-occurring disorders in combination with or as an alternative to pharmacotherapy. (See 'Integrated cognitive behavioral therapy' below.)

The evidence in support of integrated CBT for specific, co-occurring anxiety and substance use disorders is limited

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and has yielded mixed results (described below). However, based on these data, clinical trials of CBT for noncomorbid anxiety disorders or SUDs, and our clinical experience, we suggest first-line treatment of most patients with a co-occurring anxiety disorder and SUD with integrative CBT that addresses both disorders.

For patients who prefer medication treatment rather than CBT, or if CBT is unavailable, we suggest treatment of the anxiety disorder with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) over other medications. In such cases, the SUD should be treated as well. Information on the pharmacotherapy of anxiety disorders and the treatment of SUDs is discussed is separately. (See "Pharmacotherapy for posttraumatic stress disorder" and "Pharmacotherapy for social anxiety disorder" and "Pharmacotherapy for generalized anxiety disorder" and "Pharmacotherapy for panic disorder" and "Pharmacotherapy for obsessive-compulsive disorder" and "Treatment of opioid abuse and dependence" and "Cannabis use disorder: Treatment, prognosis, and long-term medical effects" and "Pharmacotherapy for alcohol use disorder" and "Psychosocial treatment of alcohol use disorder" and "Brief intervention for unhealthy alcohol and other drug use" and "Cocaine use disorder in adults: Epidemiology, pharmacology, clinical manifestations, medical consequences, and diagnosis".)

We suggest combined treatment with integrated CBT and an SSRI or SNRI rather than either intervention as monotherapy in patients with a co-occurring anxiety disorder and an SUD under the following circumstances:

If the patient's anxiety disorder has previously responded to treatment with a serotonergic antidepressantdisorder and an SUD under the following circumstances: If the anxiety disorder is severe and disabling

If the anxiety disorder is severe and disablingresponded to treatment with a serotonergic antidepressant If the disorders are accompanied by other comorbidities (eg,

If the disorders are accompanied by other comorbidities (eg, depression)If the anxiety disorder is severe and disabling If the disorders fail to respond adequately to

If the disorders fail to respond adequately to treatment with either modality as monotherapyare accompanied by other comorbidities (eg, depression) Other medications are used to treat anxiety disorders that

Other medications are used to treat anxiety disorders that do not adequately respond to SSRIs/SNRIs, and to treat SUDs. Selection of medications for treatment of co-occurring anxiety and substance-use disorders needs to take into account the abuse potential of medications prescribed as well as the potential for toxic interactions between the medications and abused substances, and between the medications and medical conditions caused by abused substances. In addition, clinicians should pro-actively address the increased risk of nonadherence to prescribed medications seen in these patients [5]. (See 'Medication issues' below.)

Medication may be needed early on particularly to help reduce anxiety symptoms while the patient is mastering behavioral ways of coping with anxiety, if there are withdrawal symptoms that will lead to relapse, and to help increase retention. Pharmacotherapies that address substance use withdrawal and craving, which may mimic or exacerbate anxiety symptoms, may be needed in addition to integrated CBT.

Treatment initiation Accumulating research evidence has challenged past beliefs that patients with a co-occurring anxiety disorder and SUD had to be abstinent for an extended period (eg, three to six months) before treating anxiety. As an example, in regard to posttraumatic stress disorder (PTSD), trials have found that addressing the trauma early in treatment results in significant improvements in anxiety symptoms as well as alcohol and drug use [6-8]. In our clinical work with outpatients with an anxiety disorder and an SUD, we have increasingly shifted to initiating treatment upon their presentation to treatment, unless hospitalization is needed for a medically supervised detoxification.

INTEGRATED COGNITIVE BEHAVIORAL THERAPY Integrated cognitive-behavioral therapy (CBT) combines cognitive and behavioral interventions for both anxiety disorders and co-occurring substance use disorders (SUDs) [4]. The components of integrative CBT in these disorders have varied in published trials, but typically include:

Education and coping skills training for both disordershave varied in published trials, but typically include: Exposure or other behavioral interventions for the anxiety

Exposure or other behavioral interventions for the anxiety disorderEducation and coping skills training for both disorders Relapse prevention for SUDs in patients who have

Relapse prevention for SUDs in patients who have achieved abstinenceor other behavioral interventions for the anxiety disorder In general, clinical trials of integrated CBT for

In general, clinical trials of integrated CBT for co-occurring anxiety disorders and SUDs (described below) have shown mixed results compared to treatment as usual or active interventions addressing one of the two comorbid disorders. Larger randomized trials are needed comparing monotherapy to integrative or sequential treatments, including medications, CBT, and other psychotherapies.

EFFICACY OF TREATMENTS FOR SPECIFIC DISORDERS Findings from clinical trials of psychotherapy and pharmacotherapy in patients with specific anxiety disorders and co-occurring substance use disorders (SUDs) are

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described here. Treatments with efficacy in these disorders when presenting without a co-occurring disorder are also briefly described and linked to topics with more detailed information.

Posttraumatic stress disorder

Integrated CBT Randomized and uncontrolled trials have found mixed results for various integrated CBT interventions in co-occurring posttraumatic stress disorder (PTSD) and SUDs, including cognitive-behavioral therapy (CBT) with and without exposure therapy for PTSD.

Seeking Safety, a manualized, integrative group CBT, developed to treat co-occurring PTSD and SUDs, provides psychoeducation and teaches coping skills. Three randomized trials in women with PTSD and SUDs found mixed evidence of efficacy for the Seeking Safety intervention in conjunction with patients usual treatment compared to treatment as usual. No difference was found in PTSD or SUD symptom reduction between Seeking Safety and two other active treatments: a health education group and a group CBT addressing only SUDs.

A trial randomly assigned 107 women with PTSD and an SUD to one of the

A

trial randomly assigned 107 women with PTSD and an SUD to one of the following: group CBT

addressing both disorders, another manualized, group CBT that addressed only substance abuse, or to treatment as usual [9]. After three months of treatment, patients receiving either of the CBT interventions

experienced reductions in substance use and in PTSD symptoms compared to patients receiving treatment as usual. Improvements were sustained at six and nine months. No differences were seen between the two CBT interventions.

A trial randomly assigned 33 adolescent girls with PTSD and an SUD to group CBT

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trial randomly assigned 33 adolescent girls with PTSD and an SUD to group CBT addressing both

disorders or to treatment as usual [10]. After three months, group CBT led to reduced substance use compared to treatment as usual. No differences between group CBT and treatment as usual were seen on

overall PTSD symptoms, but group CBT led to greater improvement on two of six subscales of an instrument measuring trauma-related symptoms.

A trial randomly assigned 49 incarcerated women with PTSD and an SUD to either group

A

trial randomly assigned 49 incarcerated women with PTSD and an SUD to either group CBT addressing

both disorders or treatment as usual alone [ 11]. Following 18 to 20 weeks of treatment, both groups

experienced reduction in PTSD symptoms and substance use, but no differences were seen between patients receiving group CBT compared to patients receiving treatment as usual.

A clinical trial randomly assigned 353 women with PTSD and an SUD to receive 12

A

clinical trial randomly assigned 353 women with PTSD and an SUD to receive 12 sessions of either group

CBT addressing both disorders, or a health education group [12]. Participants attended approximately half

of the scheduled sessions: Seeking Safety (median = 6.2 sessions) and education (median = 6.2 sessions). Large reductions in PTSD symptoms and no change in substance use were seen over the course of treatment; no significant differences were seen between treatment groups.

Two uncontrolled trials and one controlled trial in patients with co-occurring PTSD and an SUD found mixed results for interventions integrating exposure therapy for PTSD and cognitive/behavioral psychotherapy for the SUD.

In an uncontrolled trial of COPE (Concurrent Treatment of PTSD and Substance Use Disorders using

In

an uncontrolled trial of COPE (Concurrent Treatment of PTSD and Substance Use Disorders using

Prolonged Exposure), 39 patients with co-occurring PTSD and cocaine dependence were enrolled in a 16-session, manual-guided psychotherapy that consisted of imaginal and in-vivo exposure therapy to treat PTSD and cognitive-behavioral techniques to treat cocaine dependence [13]. An intent-to-treat analysis was not performed. A low participation rate was observed (only 15 of 39 patients attended at least 10 sessions). These 15 patients experienced a significant reduction in PTSD symptoms and cocaine use.

A randomized trial compared COPE plus standard treatment for SUD to standard treatment for SUD

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randomized trial compared COPE plus standard treatment for SUD to standard treatment for SUD alone

in

103 patients with PTSD and substance dependence [7]. COPE consisted of 12 sessions of

psychotherapy, including imaginal and in-vivo exposure, as well as CBT for alcohol and drug use disorders.

At nine months from the initiation of treatment, patients receiving COPE plus standard treatment experienced a greater mean decrease in PTSD symptom severity compared to patients receiving standard treatment alone (mean difference, 38.24 versus 22.14 on the Clinician-Administered PTSD Scale). No difference was seen in the severity of patients substance dependence.

Substance Dependence PTSD Therapy (SDPT) is a five-month, twice-weekly, manualized individual

Substance Dependence PTSD Therapy (SDPT) is a five-month, twice-weekly, manualized individual

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cognitive-behavioral therapy utilizing relapse prevention and coping skills training for substance abuse, and psychoeducation, stress inoculation training, and in vivo exposure for PTSD [14]. A randomized trial comparing SDPT to Twelve-Step Facilitation Therapy in the treatment of an SUD was conducted among 19 patients with cocaine abuse and PTSD [15]. No statistically significant difference was seen between treatment groups on outcomes of substance abuse or PTSD symptoms. Retention in treatment was significantly better in the SDPT group than in the Twelve-Step Facilitation group (median of 26 versus 16 sessions).

Several case reports have described positive outcomes associated with integrated CBT interventions in military veterans with co-occurring PTSD and an SUD [6,16,17].

Medication The only randomized trial of an SSRI for co-occurring PTSD and an SUD, alcohol dependence, had negative findings [18]. The 12-week trial compared sertraline to placebo in 94 individuals with these disorders. No significant difference was seen between the sertraline and placebo groups in reduction of PTSD symptoms over the course of the trial; there was a trend toward greater PTSD improvement in the sertraline group.

It has been postulated that efficacy of SSRIs in treating individuals with co-morbid PTSD and alcohol dependence may be a function of the severity of the disruption in the serotonin system. In a post-hoc cluster analysis of the previous trial [18], individuals with less severe alcohol dependence and early onset PTSD demonstrated greater improvement in alcohol use severity when treated with sertraline as compared to placebo. In contrast, individuals with more severe symptoms of alcohol dependence and late onset PTSD had poorer drinking outcomes in response to sertraline compared with placebo. Randomized trials are needed to test the efficacy of SSRIs in patients with less severe alcohol dependence and early onset PTSD.

Treatments for noncomorbid PTSD SSRIs and SNRIs have been found to be efficacious in noncomorbid PTSD. Other medications that may have efficacy in noncomorbid PTSD include atypical antipsychotics, and prazosin for sleep disruption or nightmares. Pharmacotherapy for PTSD is discussed in detail separately. (See "Pharmacotherapy for posttraumatic stress disorder".)

Psychotherapies that have been found to be efficacious in noncomorbid PTSD include cognitive-behavioral therapy that includes exposure therapy and eye movement desensitization and reprocessing therapy. Psychotherapy for PTSD is discussed in detail separately. (See "Psychotherapy for posttraumatic stress disorder".)

Generalized anxiety disorder

Integrated CBT There are no clinical trials of integrated interventions targeting both generalized anxiety disorder (GAD) and SUDs.

Medication SSRIs/SNRIs have not been tested for co-occurring GAD and an SUD. In randomized trials of patients with co-occurring GAD and SUDs, buspirone, a serotonin1A partial agonist with low abuse potential, has shown mixed results for reducing anxiety and substance use compared to placebo [19-22].

A 12-week trial randomly assigned 61 patients with anxiety and alcohol dependence to receive buspirone

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12-week trial randomly assigned 61 patients with anxiety and alcohol dependence to receive buspirone or

placebo; both groups additionally received weekly relapse prevention psychotherapy [19]. Buspirone treatment resulted in reduced anxiety, a slower return to heavy alcohol consumption, and fewer drinking days during the follow-up period compared to the placebo group.

In a trial of 51 patients with co-occurring GAD and alcohol abuse or dependence randomly

In

a trial of 51 patients with co-occurring GAD and alcohol abuse or dependence randomly assigned to

receive buspirone or placebo, patients treated with buspirone experienced greater reductions in anxiety and

in the number of days desiring alcohol compared to placebo, but no difference in alcohol consumption [20].

A trial of 65 male veterans with DSM III-R diagnosis of GAD or other nonpanic

A trial of 65 male veterans with DSM III-R diagnosis of GAD or other nonpanic forms of anxiety disorders

and alcohol dependence were randomly assigned to buspirone (45 to 60 mg/day) or placebo [21]. No differences between the buspirone and placebo groups were seen in reductions in anxiety or in alcohol use over six months of treatment.

A 12-week, randomized trial in 36 subjects receiving methadone-maintenance treatment for clinically

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12-week, randomized trial in 36 subjects receiving methadone-maintenance treatment for clinically

significant anxiety (Hamilton Anxiety Scale score of 18 or higher) compared buspirone to placebo [22]. Buspirone treatment did not significantly reduce anxiety symptoms or substance use compared to placebo.

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Treatments for noncomorbid GAD First-line treatments for non-comorbid GAD include CBT, SSRIs, or SNRIs. Other effective treatments include buspirone, benzodiazepines, tricyclic antidepressants, and pregabalin. (See "Pharmacotherapy for generalized anxiety disorder" and "Psychotherapy for generalized anxiety disorder".)

Social anxiety disorder

Integrated CBT A randomized trial did not find an integrated CBT intervention to be effective in patients with co-occurring social anxiety disorder (SAD) and an SUD. The trial randomly assigned 93 patients with SAD and alcohol dependence to receive individual CBT for alcohol dependence only, or an individual, integrative CBT addressing both disorders [23]. Counter to the hypothesis, the group receiving integrative psychotherapy for both alcohol and social anxiety disorders had worse outcomes on three of the four alcohol use indices, and no differences were seen between groups on measures of social anxiety.

Medication One small trial found an SSRI, paroxetine, to reduce symptoms of SAD when co-occurring with an SUD. The trial randomly assigned 15 outpatients with co-occurring SAD and alcohol dependence to either paroxetine or placebo [24]. After eight weeks, the paroxetine group experienced a greater reduction in SAD symptoms compared to the placebo group. No differences were seen in alcohol use.

Treatments for noncomorbid SAD First-line, effective treatments for non-comorbid, generalized SAD include SSRIs, SNRIs, or CBT. Findings from clinical trials support the efficacy of monoamine oxidase inhibitors (MAOIs), benzodiazepines, and, to a lesser extent, gabapentin and pregabalin. The use of MAOIs for the treatment of comorbid SAD and alcohol use disorders is not recommended since MAOIs and alcohol may lead to hypertensive crisis. (See "Pharmacotherapy for social anxiety disorder" and "Psychotherapy for social anxiety disorder" and 'Drug interactions' below and 'Abuse potential' below.)

Panic disorder

Integrated CBT Trials of group CBT added to standard treatment for alcohol dependence are limited and have found mixed results for anxiety and for substance use:

231 patients with co-occurring panic disorder and alcohol dependence, admitted to an inpatient alcoholism treatment program, were randomly assigned to receive either the standard alcoholism treatment program or the standard alcoholism treatment program with the addition of group CBT for panic disorder [25 ]. The standard alcoholism program was group-oriented and included relaxation training and discussion of 25]. The standard alcoholism program was group-oriented and included relaxation training and discussion of how to cope with stress. While both groups experienced improvement, no differences were seen between the CBT and non-CBT groups on most measures of panic disorder symptoms and alcohol use at 3, 6, and 12 months post-treatment.

In a nonrandomized, unblinded study, 43 patients with co-occurring panic disorder and alcohol dependence, admitted to an alcoholism treatment partial program, were additionally treated with integrated group CBT [26 ]. The CBT program consisted of three modules psychoeducation, cognitive restructuring, and exposure and 26]. The CBT program consisted of three modules psychoeducation, cognitive restructuring, and exposure and addressed issues at the interface between the comorbid disorders. Outcomes of 31 patients who completed both the alcohol treatment and group CBT were compared to a control group of 17 patients with panic disorder and alcohol dependence who completed the alcoholism treatment program but did not receive group CBT. Patients who received group CBT were less likely to meet criteria for panic disorder at the end of four months of treatment. Alcohol relapse rates did not differ between groups, but patients who received CBT had fewer drinks and fewer drinking binges.

Medications No clinical trials have investigated the efficacy of medications for co-occurring panic disorder and SUDs.

Treatments for noncomorbid panic disorder First-line treatments for non-comorbid panic disorder include SSRIs or CBT. Other effective treatments include SNRIs, tricyclic antidepressants, and benzodiazepines. (See 'Medication issues' below and "Pharmacotherapy for panic disorder" and "Psychotherapy for panic disorder".)

Obsessive-compulsive disorder

Integrative CBT One randomized trial found the combination of CBT for obsessive compulsive disorder (OCD) and behavioral therapy for a co-occurring SUD to be effective [27] The trial randomly assigned 60 patients

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with co-occurring OCD and an SUD to either exposure and response prevention therapy (a type of CBT used for OCD) in conjunction with behavioral therapy for the SUD, behavioral therapy for the SUD only, or behavioral therapy for the SUD combined with progressive muscle relaxation (as a control intervention). The group receiving CBT for OCD and behavioral therapy for the SUD experienced a greater reduction in OCD symptoms, a higher abstinence rate, and greater treatment retention compared to the other two groups.

Medication There have been no randomized trials of medications for co-occurring OCD and SUDs. A case report of a patient with OCD and alcohol dependence found decreased craving and alcohol consumption to be associated with treatment with paroxetine and gabapentin, but the medications impact on OCD symptoms was unclear [28].

Treatments for noncomorbid OCD First-line, effective treatments for noncomorbid OCD include CBT (in particular, exposure and response prevention) and SSRIs. Other effective treatments include clomipramine and venlafaxine. (See "Pharmacotherapy for obsessive-compulsive disorder" and "Psychotherapy for obsessive- compulsive disorder".)

Substance use disorders For patients with a co-occurring anxiety disorder and SUD, we suggest first-line treatment with an integrative cognitive behavioral therapy (CBT) that addresses both disorders over other treatments. Pharmacotherapy for one or both disorders can be used if integrative CBT is not available or if patients prefer medication treatment rather than psychotherapy. Pharmacotherapy for SUDs is discussed separately. Toxic interactions between medications used in anxiety disorders and abused substances are discussed below. (See "Pharmacotherapy for alcohol use disorder" and "Treatment of opioid abuse and dependence" and "Cocaine use disorder in adults: Epidemiology, pharmacology, clinical manifestations, medical consequences, and diagnosis" and "Cannabis use disorder: Treatment, prognosis, and long-term medical effects" and 'Drug interactions' below.)

Integrative CBT The trials of integrative CBT in patients with co-occurring anxiety disorders and SUDs, described above under individual anxiety disorders, found mixed results for changes in SUD severity. These trials included several anxiety disorders and varied abused substances. (See 'Posttraumatic stress disorder' above and 'Generalized anxiety disorder' above and 'Social anxiety disorder' above and 'Panic disorder' above and 'Obsessive-compulsive disorder' above.)

Medication The efficacy of common medications for alcohol dependence has not been studied in patients with alcohol dependence and a co-occurring anxiety disorder; however, a study of naltrexone and disulfiram in this population found the medications to be safe and well tolerated [9].

MEDICATION ISSUES

Drug interactions Before prescribing a medication for a patient with co-occurring anxiety disorder and substance use disorder (SUD), potential toxic interactions between prescribed medications and alcohol or other drugs of abuse must be considered [29]. Detrimental effects may occur when the substance consumed alters the pharmacokinetic properties (ie, interferes with the metabolism) of the medication or pharmacodynamic properties (ie, enhances the effects) of the medication. Clinically important interactions between psychotropic medications and commonly abused substances include [29]:

Anxiolytics

Benzodiazepines should be avoided in the treatment of anxiety co-occurring with opioid abuse or dependence, as they have led to serious adverse events in such patients, including respiratory depression and accidental overdose.and commonly abused substances include [ 29 ]: Anxiolytics Benzodiazepines interact significantly with alcohol in that

Benzodiazepines interact significantly with alcohol in that both facilitate inhibition at GABA receptors and result in additive central nervous system depression causing sedation and respiratory depression.including respiratory depression and accidental overdose. Few reports of toxicity between buspirone and substances

Few reports of toxicity between buspirone and substances of abuse have been reported although alcohol may increase the sedative effects buspirone and substances of abuse have been reported although alcohol may increase the sedative effects of buspirone. When buspirone is used in a patient with co-occurring anxiety disorder and alcohol use disorder, the dose should be titrated up carefully and the patient response should be monitored.

Antidepressants

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Toxic interactions between selective serotonin reuptake inhibitors (SSRIs) and alcohol/other drugs of abuse are relatively low.Isocarboxazid , a monoamine oxidase inhibitor (MAOI), should

Isocarboxazid, a monoamine oxidase inhibitor (MAOI), should be avoided in patients suspected of stimulant abuse, , a monoamine oxidase inhibitor (MAOI), should be avoided in patients suspected of stimulant abuse, as amphetamines can increase the risk of hypertensive crisis in patients taking the medication.

Potential interactions between MAOIs and opioids include respiratory distress, hypo/hypertension, convulsions, and tachycardia. MAOIs should be avoided in patients suspected of opioid abuse [30 ]. 30].

The use of MAOIs in the treatment of a disorder co-occurring with an alcohol use disorder is not recommended, because MAOIs and alcohol may lead to hypertensive crisis.be avoided in patients suspected of opioid abuse [ 30 ]. The use of tricyclic antidepressants

The use of tricyclic antidepressants (TCAs) is not recommended in patients suspected of alcohol abuse, because fatal interactions between tricyclic antidepressants, amitriptyline and doxepin , and alcohol have been reported [ 31 ]. amitriptyline and doxepin, and alcohol have been reported [31].

TCAs should be avoided in patients suspected of stimulant abuse. Stimulants may increase blood levels of TCAs, increasing the risk of cardiotoxicity.and doxepin , and alcohol have been reported [ 31 ]. TCAs lower seizure threshold and

TCAs lower seizure threshold and should be avoided in patients undergoing opioid and/or alcohol withdrawal.blood levels of TCAs, increasing the risk of cardiotoxicity. Other Gabapentin taken with alcohol and/or opioids

Other

Gabapentin taken with alcohol and/or opioids may increase the risk for sedation, dizziness and drowsiness. An taken with alcohol and/or opioids may increase the risk for sedation, dizziness and drowsiness. An expanding literature suggests that the GABAergic anticonvulsant pregabalin does not exacerbate the symptoms of alcohol intoxication [32].

Prazosin should be avoided in patients suspected of alcohol abuse as concurrent use of prazosin, an should be avoided in patients suspected of alcohol abuse as concurrent use of prazosin, an alpha- adrenergic antagonist, and alcohol may increase the risk of hypotension [33].

Medical conditions Adverse reactions to prescribed medications can arise from medical conditions, including medical conditions related to SUDs. Examples include:

Among patients with alcohol use disorders, a careful monitoring of liver function may be needed for medications that undergo extensive hepatic metabolism (eg, venlafaxine , buspirone ) [ 34 ]. venlafaxine, buspirone) [34].

Lower or less frequent doses of sertraline and citalopram are recommended for alcohol dependent patients presenting with severe liver disease. sertraline and citalopram are recommended for alcohol dependent patients presenting with severe liver disease.

Duloxetine, an antidepressant, should not be prescribed to alcohol dependent patients presenting with liver disease, , an antidepressant, should not be prescribed to alcohol dependent patients presenting with liver disease, as it may exacerbate the condition.

Abuse potential Clinicians should consider the abuse potential of medications used to treat anxiety disorders co-occurring with SUDs.

Benzodiazepines are widely used in the treatment of anxiety disorders, but may be abused and can lead to dependence. Patients with current substance dependence should not be prescribed benzodiazepines, except for detoxification. Use of benzodiazepines in patients who are no longer abusing substances is not absolutely contraindicated. Benzodiazepine use in such cases should be accompanied by increased visit frequency and prescription monitoring.

There is an absence of data to support a specific duration of abstinence prior to prescribing a benzodiazepine. No matter how long the period, an increased risk of abuse and dependence is likely among patients with a prior history of dependence. However, a longer abstinence (eg, 12 months) may lessen the risk.

Treatment lasting months or more is likely to lead to physiological dependence and consequent withdrawal symptoms if discontinued too quickly.

Medications with low abuse potential that are alternatives to benzodiazepines include:

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Serotonergic antidepressants in several anxiety disordersPregabalin and buspirone in general anxiety disorder

Pregabalin and buspirone in general anxiety disorder (GAD), though buspirone has shown mixed results in clinical and buspirone in general anxiety disorder (GAD), though buspirone has shown mixed results in clinical trials of GAD with a co-occurring SUD.

Gabapentin and pregabalin in social anxiety disorder and pregabalin in social anxiety disorder

Gabapentin may be effective in alcohol withdrawal, though findings from clinical trials are mixed. may be effective in alcohol withdrawal, though findings from clinical trials are mixed.

Trials of these medications in co-occurring anxiety disorders and SUDs, where available, are described above; detailed information on their efficacy and administration in noncomorbid disorders is described separately. (See 'Efficacy of treatments for specific disorders' above and "Pharmacotherapy for generalized anxiety disorder", section on 'Buspirone' and "Pharmacotherapy for generalized anxiety disorder", section on 'Pregabalin' and "Pharmacotherapy for social anxiety disorder", section on 'Other agents' and "Ambulatory alcohol detoxification", section on 'Anticonvulsants'.)

Adherence Patients with active SUDs are at increased risk for medication nonadherence [35,36], potentially limiting treatment outcomes for both the anxiety disorder and SUD. Poor adherence may stem from multiple causes, including:

Poor psychosocial functioning, housing, legal issues, impaired judgment, cognitive dysfunction, and disorganization from substance abuse.Poor adherence may stem from multiple causes, including: Individuals in treatment for SUDs may regard pharmacotherapy

Individuals in treatment for SUDs may regard pharmacotherapy as an individual failure, not distinguishing between the need to abstain from drugs of abuse and the potential utility of therapeutic medications.dysfunction, and disorganization from substance abuse. Patients may increase their dosage of therapeutic

Patients may increase their dosage of therapeutic medications in an attempt to self-medicate in response to stress [37 ]. 37].

Clinicians should inquire about the patient s previous experience with medication. Illustrative questions include:

What have you been prescribed and why?experience with medication. Illustrative questions include: Were these medications helpful and, if so, how? Did the

Were these medications helpful and, if so, how?questions include: What have you been prescribed and why? Did the medications cause adverse effects? Under

Did the medications cause adverse effects?and why? Were these medications helpful and, if so, how? Under what conditions were the medications

Under what conditions were the medications discontinued?and, if so, how? Did the medications cause adverse effects? Did you take the medication as

Did you take the medication as prescribed?Under what conditions were the medications discontinued? What concerns do you have about medication? The clinician

What concerns do you have about medication?discontinued? Did you take the medication as prescribed? The clinician should provide direct and detailed information

The clinician should provide direct and detailed information regarding the importance of medication adherence in their treatment. Explain that the beneficial effects of medication can emerge gradually, and over what time period, so that patients understand what to expect.

Adherence to medications should be carefully monitored at each visit by self-report, collateral report if possible (eg, if a parent or spouse observes patient taking disulfiram each day), and biological tests if available. Nonadherence should be addressed with the patient.

The patient should be cautioned that he or she should not take a passive stance with regard to treatment because a medication has been prescribed; patients should understand that they will need to be an active participant in psychotherapy in order to develop healthy coping skills.

Motivational interviewing has been used to address treatment nonadherence in patients with an SUD, focusing on ambivalent feelings and thoughts that patients may have about prescribed medications and their conditions. (See "Motivational interviewing for substance use disorders".)

Such beliefs may include:

He or she should be able to stay sober and handle anxiety symptoms without a medicationfor substance use disorders" .) Such beliefs may include: Taking a medication is a weakness 8

Taking a medication is a weaknessinclude: He or she should be able to stay sober and handle anxiety symptoms without a

Treatment of co-occurring anxiety disorders and substance use disorders

He or she wants to be completely drug free drug free

SUMMARY AND RECOMMENDATIONS

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For most patients with a co-occurring anxiety disorder and substance use disorder (SUD), we suggest first-line treatment with an integrative cognitive-behavioral therapy (CBT) that addresses both disorders (Grade 2C ). Grade 2C).

(See 'Posttraumatic stress disorder' above.) 'Posttraumatic stress disorder' above.)

(See 'Generalized anxiety disorder' above.) 'Generalized anxiety disorder' above.)

(See 'Social anxiety disorder' above.) 'Social anxiety disorder' above.)

(See 'Panic disorder' above.) 'Panic disorder' above.)

(See 'Obsessive-compulsive disorder' above.) 'Obsessive-compulsive disorder' above.)

For patients who prefer medication treatment rather than CBT, or if CBT is unavailable, we suggest first-line treatment of the anxiety disorder with a selective serotonin reuptake inhibitor (SSRI) or a serotonin- norepinephrine reuptake inhibitor (SNRI) over other medications (Grade 2C ). In such cases, the SUD should be treated as well. Detailed information Grade 2C). In such cases, the SUD should be treated as well. Detailed information on treatment of SUDs and on pharmacotherapy of anxiety disorders is discussed separately. (See "Pharmacotherapy for posttraumatic stress disorder" and "Pharmacotherapy for social anxiety disorder" and "Pharmacotherapy for generalized anxiety disorder" and "Pharmacotherapy for panic disorder" and "Pharmacotherapy for obsessive-compulsive disorder" and "Treatment of opioid abuse and dependence" and "Cannabis use disorder: Treatment, prognosis, and long-term medical effects" and "Pharmacotherapy for alcohol use disorder" and "Psychosocial treatment of alcohol use disorder" and "Brief intervention for unhealthy alcohol and other drug use" and "Cocaine use disorder in adults:

Epidemiology, pharmacology, clinical manifestations, medical consequences, and diagnosis".)

We suggest combined treatment with integrative CBT and an SSRI or SNRI rather than CBT or a serotonergic antidepressant along in patients with a co-occurring anxiety disorder and an SUD under the following circumstances (Grade 2C ): Grade 2C):

If the patient's anxiety disorder has previously responded to treatment with a serotonergic antidepressantand an SUD under the following circumstances ( Grade 2C ): If the anxiety disorder is

If the anxiety disorder is severe and disablingresponded to treatment with a serotonergic antidepressant If the disorders are accompanied by other comorbidities (eg,

If the disorders are accompanied by other comorbidities (eg, depression)If the anxiety disorder is severe and disabling If the disorders fail to respond adequately to

If the disorders fail to respond adequately to treatment with either modality as monotherapyare accompanied by other comorbidities (eg, depression) (See 'Approach to treatment' above.) Selection of

(See 'Approach to treatment' above.)

Selection of medications for treatment of co-occurring anxiety and substance-use disorders should take into account the abuse potential of medications prescribed as well as the potential for toxic interactions between the medications and abused substances, and between the medications and medical conditions caused by commonly abused substances. (See 'Medication issues' above.) 'Medication issues' above.)

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Topic 14344 Version 1.0