Common Comorbidities with Substance Use Disorders Research Report
What are the treatments for comorbid substance use disorder and mental health conditions?

Integrated treatment for comorbid drug use disorder and mental illness has been found to be consistently superior compared with separate treatment of each diagnosis.3,81–83 Integrated treatment of co-occurring disorders often involves using cognitive behavioral therapy strategies to boost interpersonal and coping skills and using approaches that support motivation and functional recovery.81

Patients with comorbid disorders demonstrate poorer treatment adherence84 and higher rates of treatment dropout3,82 than those without mental illness, which negatively affects outcomes. Nevertheless, steady progress is being made through research on new and existing treatment options for comorbidity.74,81–83,85 In addition, research on implementation of appropriate screening and treatment within a variety of settings, including criminal justice systems, can increase access to appropriate treatment for comorbid disorders.86 

Treatment of comorbidity often involves collaboration between clinical providers and organizations that provide supportive services to address issues such as homelessness, physical health, vocational skills, and legal problems.87 Communication is critical for supporting this integration of services. Strategies to facilitate effective communication may include co-location, shared treatment plans and records, and case review meetings.87 Support and incentives for collaboration may be needed, as well as education for staff on co-occurring substance use and mental health disorders.

Treatment for Youth

As mentioned previously, the onset of mental illness and substance use disorders often occurs during adolescence, and people who develop problems earlier typically have a greater risk for severe problems as adults. Given the high prevalence of comorbid mental disorders and their adverse impact on SUD treatment outcomes, SUD programs for adolescents should screen for comorbid mental disorders and provide treatment as appropriate.21,23,88

Research indicates that some mental, emotional, and behavioral problems among youth can be prevented or significantly mitigated by evidence-based prevention interventions.89 These interventions can help reduce the impact of risk factors for substance use disorders and other mental illnesses, including parental unemployment, maternal depression, child abuse and neglect, poor parental supervision, deviant peers, deprivation, poor schools, trauma, limited health care, and unsafe and stressful environ­ments. Implementation of policies, programs, and practices that decrease risk factors and increase resilience can help reduce both substance use disorders and other mental illnesses, potentially saving billions of dollars in associated costs related to health care and incarceration.89

Other evidence-based interventions emphasize strengthening protective factors to enhance young people’s well-being and provide the tools to process emotions and avoid behaviors with negative consequences. Key protective factors include supportive family, school, and community environ­ments.

In addition to the treatment options discussed in this research report, the following treatments have been shown to be effective for children and adolescents:

  • Multisystemic Therapy (MST). MST targets key factors that are associated with serious antisocial behavior in children and adolescents with substance use disorders, such as attitudes, family, peer pressure, school and neighborhood culture.22,24
  • Brief Strategic Family Therapy (BSFT). BSFT targets family interactions that are thought to maintain or exacerbate adolescent substance use disorder and other co-occurring problem behaviors such as conduct problems, oppositional behavior, delinquency, associating with antisocial peers, aggressive and violent behavior, and risky sexual behaviors.90
  • Multidimensional Family Therapy (MDFT). MDFT, a comprehensive intervention for adolescents, focuses on multiple and interacting risk factors for substance use disorders and related comorbid conditions. This therapy addresses adolescents’ interpersonal and relationship issues, parental behaviors, and the family environment. Families receive assistance with navigating school and social service systems, as well as the juvenile justice system if needed. Treatment includes individual and family sessions.91


Effective medications exist for treating opioid, alcohol, and nicotine use disorders and for alleviating the symptoms of many other disorders.62,74,83 While most have not been well studied in comorbid populations, some medications may help treat multiple problems. For example, bupropion is approved for treating depression and nicotine dependence. For more information, see the table below.

Pharmacotherapies Used to Treat Alcohol, Nicotine, and Opioid Use Disorders
Medication Use Dosage Form DEA Schedule* Application
Buprenorphine-Naloxone Opioid use disorder Sublingual or buccal film buprenorphine/naloxone 2mg/0.5mg, 4mg/1mg, 8mg/2mg, and 12mg/3mg

Sublingual tablet: buprenorphine/naloxone 1.4mg/0.36mg, 2mg/0.5mg, 2.9/0.71mg, 5.7mg/1.4mg, 8mg/2mg, 8.6mg/2.1mg, 11.4mg/2.9mg

Buccal film: buprenorphine/naloxone 2.1mg/0.3mg, 4.2mg/0.7mg, 6.3mg/1mg
CIII Used for detoxification and maintenance of abstinence for individuals aged 16 or older.
Buprenorphine Hydrochloride Opioid use disorder Sublingual tablet: 2mg, 4mg, 8mg, and 12mg

Probuphine® implants 80mgx4 implants for a total of 320mg
CIII This formulation is indicated for treatment of opioid dependence and is preferred for induction. However, it is considered the preferred formulation for pregnant patients, patients with hepatic impairment, and patients with sensitivity to naloxone. It is also used for initiating treatment in patients transferring from methadone, in preference to products containing naloxone, because of the risk of precipitating withdrawal in these patients. For those already stable on low to moderate dose buprenorphine. The administration of the implant dosage form requires specific training and must be surgically.
Methadone Opioid use disorder Tablet: 5mg, 10mg
Tablet for suspension: 40mg
Oral concentrate: 10mg/mL
Oral solution: 5mg/5mL, 10mg/5mL
Injection: 10mg/mL
CII Providers using this medication must be linked to a federally certified Opioid Treatment Program. Under federal regulations, it can be used in persons under age 18 at the discretion of an Opioid Treatment Program physician.
Naltrexone Opioid use disorder; alcohol use disorder Tablets: 25mg, 50mg, and 100mg
Extended-release injectable suspension: 380mg/vial
Not scheduled under the Controlled Substances Act Provided by prescription; naltrexone blocks opioid receptors, reduces cravings, and diminishes the rewarding effects of alcohol and opioids. Extended-release injectable naltrexone is recommended to prevent relapse to opioids or alcohol. The prescriber need not be a physician, but must be licensed and authorized to prescribe by the state.
Acamprosate Alcohol use disorder Delayed-release tablet: 333mg Not scheduled under the Controlled Substances Act Provided by prescription; acamprosate is used in the maintenance of alcohol abstinence. The prescriber need not be a physician, but must be licensed and authorized to prescribe by the state.
Disulfiram Alcohol use disorder Tablet: 250mg, 500mg Not scheduled under the Controlled Substances Act When taken in combination with alcohol, disulfiram causes severe physical reactions, including nausea, flushing, and heart palpitations. The knowledge that such a reaction is likely if alcohol is consumed acts as a deterrent to drinking.
Nicotine Replacement Therapies Nicotine use disorder Transdermal patches: 7-22 mg/day
Gum: 18-48 mg/day
Lozenges: 40-80 mg/day
Inhalers: Variable dosing Nasal spray: Up to 40 mg/day
Not scheduled under the Controlled Substances Act Nicotine replacement therapy helps alleviate withdrawal symptoms in the short term, and patients with severe nicotine use disorder might benefit from more long-term use.
Bupropion HCl Nicotine use disorder Tablet: 150 mg/day for three days, then increase to 300 mg/day for 7-12 weeks Not scheduled under the Controlled Substances Act Bupropion HCl is an antidepressant that has also been shown to assist with nicotine cessation, although the mechanism of action is not understood.
Varenicline Nicotine use disorder Tablet: 0.5 mg/day for three days; 0.5 mg twice a day for days 4-7; then 1.0 mg twice a day through week 12 Not scheduled under the Controlled Substances Act Varenicline helps reduce nicotine cravings.
Source: The Surgeon General’s report and National Cancer Institute, Cigarette Smoking: Health Risks and How to Quit

Behavioral Therapies

Behavioral treatment (alone or in combination with medications) is a cornerstone to successful long-term outcomes for many individuals with drug use disorders or other mental illnesses.3,81–83,85 Several strategies have shown promise for treating specific comorbid conditions.

  • Cognitive Behavioral Therapy (CBT)
    CBT is designed to modify harmful beliefs and maladaptive behaviors and shows strong efficacy for individuals with substance use disorders. CBT is the most effective psychotherapy for children and adolescents with anxiety and mood disorders.22,24,88
  • Dialectical Behavior Therapy (DBT)
    DBT is designed specifically to reduce self-harm behaviors including suicidal attempts, thoughts, or urges; cutting; and drug use. It is one of the few treatments effective for individuals who meet the criteria for borderline personality disorder.92
  • Assertive Community Treatment (ACT)
    ACT programs integrate behavioral treatments for severe mental illnesses such as schizophrenia and co-occurring substance use disorders. ACT is differentiated from other approaches to case management through factors such as a smaller caseload size, team management, outreach emphasis, a highly individualized approach, and an assertive approach to maintaining contact with patients.93
  • Therapeutic Communities (TCs)
    TCs are a common form of long-term residential treatment for substance use disorders. They focus on the “resocialization” of the individual, often using broad-based community programs as active components of treatment. TCs are appropriate for populations with a high prevalence of co-occurring disorders such as criminal justice-involved persons, individuals with vocational deficits, vulnerable or neglected youth, and homeless individuals.86 In addition, some evidence suggests that TCs may be helpful for adolescents who have received treatment for substance use and addiction.94
  • Contingency Management (CM) or Motivational Incentives (MI)
    CM/MI is used as an adjunct to treatment. Voucher or prize-based systems reward patients who practice healthy behaviors and reduce unhealthy behaviors, including smoking and drug use. Incentive-based treatments are effective for improving treatment compliance and reducing tobacco and other drug use, and can be integrated into behavioral health treatment programs for people with co-occurring disorders.95
  • Exposure Therapy
    Exposure therapy is a behavioral treatment for some anxiety disorders (phobias and PTSD) that involves repeated exposure to a feared situation, object, traumatic event, or memory. This exposure can be real, visualized, or simulated, and is always contained in a controlled therapeutic environment. The goal is to desensitize patients to the triggering stimuli and help them develop coping mechanisms, eventually reducing or even eliminating symptoms. Several studies suggest that exposure therapy may be helpful for individuals with comorbid PTSD and cocaine use disorder, although retention in treatment is a challenge.57
  • Integrated Group Therapy (IGT)
    IGT is a treatment developed specifically for patients with bipolar disorder and substance use disorder, designed to address both problems simultaneously.96 This therapy is largely based on CBT principles and is usually an adjunct to medication. The IGT approach emphasizes helping patients understand the relationship between the two disorders, as well as the link between thoughts and behaviors, and how they contribute to recovery and relapse.96
  • Seeking Safety (SS)
    Seeking Safety is a present-focused therapy aimed at treating trauma-related problems (including PTSD) and substance use disorder simultaneously. Patients learn behavioral skills for coping with trauma/post-traumatic stress disorder and substance use disorder.97
  • Mobile Medical Application
    In 2017, the Food and Drug Administration approved the first mobile medical application to help treat substance use disorders. The intention is for patients to use it with outpatient therapy to treat alcohol, cocaine, marijuana, and stimulant use disorders; it is not intended to treat opioid dependence. The device delivers CBT to patients to teach skills that aid in the treatment in substance use disorders and increase retention in outpatient therapy programs.98