What is the pharmacological treatment approach for a patient with cocaine use disorder and a history of substance-induced psychosis?

Pharmacological Treatment of Cocaine and Stimulant Use Disorder

No FDA-approved medications exist for cocaine or stimulant use disorder, and current evidence does not support pharmacotherapy as first-line treatment in primary care settings. 1, 2 Psychosocial interventions, specifically the combination of Contingency Management (CM) plus Community Reinforcement Approach (CRA), represent the evidence-based standard of care. 2, 3

First-Line Treatment: Psychosocial Interventions

The combination of CM plus CRA is the most effective treatment approach, with a number needed to treat (NNT) of 3.7 for achieving abstinence. 2 This combined intervention addresses both immediate behavioral reinforcement and underlying psychological/social factors maintaining addiction. 2

Components of the Combined Approach:

• Contingency Management (CM): Provides tangible rewards (vouchers or prizes) contingent upon drug-free urine samples, creating immediate positive reinforcement for abstinence. 2, 4

• Community Reinforcement Approach (CRA): Multi-layered intervention involving functional analysis, coping-skills training, and social, familial, recreational, and vocational reinforcements. 2, 4

• Critical rationale: CM alone shows efficacy during active treatment but effects are not sustained at long-term follow-up, necessitating the comprehensive CRA component. 2, 4

Pharmacological Considerations

Despite continued research efforts, no pharmacologic treatment for stimulant dependence can be recommended for use in the primary care setting. 1 The evidence base remains insufficient to support routine medication use. 5, 6

Investigational Medications (Low-Quality Evidence):

When psychosocial interventions alone are insufficient, the following medications have shown the most promise but remain investigational:

• Prescription amphetamines (mixed amphetamine salts, lisdexamphetamine, dextroamphetamine): Most consistent evidence for promoting sustained abstinence in cocaine use disorder, particularly at higher doses [RR = 2.44,95% CI (1.66,3.58)]. 7 However, these remain investigational and should only be considered as adjuncts to CM plus CRA, never as monotherapy. 2

• Disulfiram: Shown the most consistent effect to reduce cocaine use across multiple studies, but remains investigational. 2

• Modafinil, bupropion, and topiramate: May improve abstinence but have low strength of evidence. 2, 5, 6

• Important caveat: All pharmacological agents must be combined with concurrent psychosocial interventions (CM plus CRA), as combined treatment shows superior outcomes to medication alone. 4

Special Consideration: Substance-Induced Psychosis

For patients with cocaine use disorder and history of substance-induced psychosis:

• Cocaine-induced psychotic disorder (CIPD) occurs in up to 86.5% of patients in some settings and requires specific management. 8

• Acute management: Supportive measures are the first approach, but antipsychotic use is often necessary due to clinical severity. 9

• Second-generation antipsychotics (such as asenapine) may be beneficial for managing acute CIPD, though evidence is limited to case reports. 9

• Risk factors for CIPD: High cocaine consumption, cannabis dependence history, antisocial personality disorder, non-intranasal routes of administration, and ADHD comorbidity. 8

• Critical point: The primary treatment remains CM plus CRA for the underlying cocaine use disorder, with antipsychotics reserved for acute psychotic episodes. 2, 3

Alternative Psychosocial Interventions

When CM plus CRA is unavailable:

• Cognitive Behavioral Therapy (CBT): More acceptable than treatment as usual but not significantly more efficacious for abstinence (NNT = 10.5). 2 Should be delivered concurrently with any pharmacotherapy, not sequentially. 2, 4

• 12-step programs: Not supported by strong evidence as standalone treatment but may be beneficial as adjunct for maintaining long-term abstinence. 2, 3

Monitoring Requirements

Regular urine drug screening is essential for implementing CM effectively and should be conducted throughout treatment. 2, 3

Cardiovascular Monitoring:

• Assess for cardiac complications including coronary artery spasm, tachycardia, increased blood pressure, and risk of myocardial infarction. 3

• Continued cardiovascular monitoring is necessary throughout treatment given cocaine's cardiac effects. 3

• For patients with cocaine-related left ventricular dysfunction who have demonstrated abstinence for >6 months, standard therapy including β-blockers may be considered. 3

Additional Monitoring:

• Evaluate for co-occurring psychiatric conditions, which are common and may complicate treatment. 1, 3

• Assess for neurological disorders, cognitive deficits, and blood-borne viral infections. 2

Common Pitfalls to Avoid

• Relying solely on CM without CRA: Leads to relapse after treatment completion as underlying factors are not addressed. 2, 4

• Using non-contingent rewards: Providing rewards regardless of drug use status has not shown effectiveness. 2

• Inadequate long-term follow-up: Critical for sustained recovery, with at least 3 months recommended for longitudinal assessment. 2, 4

• Pharmacotherapy as monotherapy: Never use medications alone without concurrent psychosocial interventions. 2, 4

• Overlooking co-occurring conditions: Mental health disorders and medical complications require integrated treatment approaches. 1, 3

Referral Indications

Refer to addiction specialists when:

• Co-occurring alcohol or benzodiazepine abuse is present. 1

• Uncontrolled or unstable psychiatric disorder exists. 1

• Treatment in the office setting has been ineffective. 1

• Comorbid chronic pain requires opioid therapy. 1