Pharmacotherapy of Dual Disorders

Medication

Substance of abuse

Antidepressants

Antipsychotics

Benzodiazepines

Alcohol

Sedation ↑, Seizure threshold ↓

Sedation ↑, Seizure threshold ↓,

Sedation ↑ and motor performance ↓ with some BZD

Opioids

All toxic opioid effects ↑ through CYP450 inhibition:

Methadone, Codeine and buprenorphine serum levels ↑ through 3A4 and 2D6 inhibition by Fluvoxamine, Fluoxetine; Methadone and codeine ↑ through 2D6 inhibition by paroxetine, sertraline, citalopram, escitalopram, bupropion, doxepin

Methadone and codeine ↑ through 2D6 inhibition by perphenazine, chlorpromazine, haloperidol

BZD are metabolized mainly by CYP450 3A4, 3A5, 2C19 and thus can interact with opioid metabolism.

Sedation ↑ (up to apnea). There is an extensive record of deaths related to parallel consumption of opioids and BZD

Amphetamines, Cocaine

↑ Risk of serotonin syndrome with SSRI, SNRI, and MAO-I. Cocaine inhibits venlafaxine and trimipramine metabolism via CYP 2D6

Amphetamines and cocaine may antagonize the antipsychotic effects. Cocaine increases serum concentration of zuclopenthixol and iloperidone via CYP 2D6 inhibition

No relevant interaction reported

Cannabis

Severe tachycardia with TCA due to combined anticholinergic action

Risk of tachycardia with neuroleptics with high anticholinergic potency (e.g., clozapine, chlorpromazine). Cannabis may antagonize antipsychotic effects (but may also improve extrapyramidal motor symptoms)

Potential of synergistic action on sedation and respiratory depression

In general, the use of anticraving drugs can also be recommended in dual disorders, based on a small empirical basis. Table 19.2 summarizes the available evidence to reduce alcohol consumption for different medication used in SUD with selected comorbid conditions.

Table 19.2

Summary of the evidence from RCTs for pharmacological treatments to reduce SUD (alcohol intake-related outcome measures) in patients with comorbid mental disorders

	Comorbid mental disorder
	Any anxiety disorder	Unipolar depression	Bipolar disorder	Schizophrenia
Positive evidence from RCTs	Naltrexone (in PTSD)	Fluoxetine, Acamprosate	Valproate	Naltrexone
Inconsistent evidence from RCTs	Buspirone, Paroxetine	Sertraline	–	–
Negative evidence from RCTS	Venlafaxine	Desipramine, Nefazodone, Imipramine	Lithium	−

RCTs Randomized controlled trials, SUD Substance use disorder, PTSD Posttraumatic stress disorder. Evidence for anticraving medication in Italics

Antidepressants should be used in unipolar affective disorders, with no particular drug to be favored. In anxiety disorders, serotonergic drugs including venlafaxine may be the primary drugs of choice. Novel drugs such as CRF1 antagonists are currently studied in anxious alcoholics. Recommendations for schizophrenia and bipolar disorders are more difficult. Compliance is a critical issue in both. Novel antipsychotics with a lower risk of EPMS may be favored to enhance compliance. Dual disorder patients may have an increased risk for EPMS. For schizophrenia the evidence is relatively best for clozapine. Injectable antipsychotics are an alternative strategy to enhance compliance. And finally: if possible, drugs with an abuse potential should be avoided, if possible, or its use strictly limited.

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