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Chapter: Essentials of Psychiatry: Pharmacotherapies for Substance Abuse

Pharmacotherapies for Substance Abusers with Additional Types of Psychiatric Illness

Pharmacotherapies for Substance Abusers with Additional Types of Psychiatric Illness

Pharmacotherapies for Substance Abusers with Additional Types of Psychiatric Illness


Rates of substance abuse are higher than expecte dmang patients with psychiatric disorders, and psychiatric disorders are higher than expected among people with substance abuse disorders.


Clinical experience shows that:


·                 treatment should be administered by professionals with con-siderable experience in both general psychiatry and chemical dependence;


·                 it is unrealistic to insist on abstinence as a precondition for treatment;


·                 some symptom stability may be necessary before reductions in substance use are evident;

·                 abstinence is not a prerequisite for safe and effective treatment with most psychotropic agents;


·                 unless treated as a disorder in itself, a substance abuse tends to persist after comorbid psychopathology is effectively treated.


This section summarises the management of particular psychi-atric illnesses complicated by substance use and some relevant drug interactions.


Drug Treatment for Specific Psychiatric Disorders


There is controversy about the stage at which a mood disor-der iunduced by substance abuse becomes a major depressive episode. Most specialists will diagnose a second disorder in a patient who presents with a depressive syndrome only after a 2 week period of sobriety. However, evidence from clinical trials shows that antidepressants may be effective in patients who are not initially abstinent. Clinical judgment is therefore important and, if a nonabstinent patient has persistent depression, a trial of antidepressant therapy may be carried out. Concurrent use of an antidepressant and a substance of abuse may increase the risk of cardiotoxicity (arrhythmias), neurologic effects (seizures) or death from intentional overdose. These risks are greatest with the tricyclic antidepressants whereas the selective serononin reuptake inhibitors have a safer pharmacologic profile. Patients should always be discouraged from substance abuse but signifi-cant numbers of those taking antidepressants also use alcohol and other potential drugs of abuse in moderation without harm. Antidepressants seem to have a low risk of abuse, though abuse of amitriptyline (for its sedative effects) and fluoxetine (for stimu-lant effects) has been reported.


Substance abuse or dependence is a common complication of schizophrenia and psychotic symptoms occurring during drug intoxication or withdrawal also complicate the diagnosis of schiz-ophrenia. An especially high degree of psychiatric sophistication and patience is necessary for this group of patients. Long-term studies (.one year) show that patients with schizophrenia and substance abuse need an energetic treatment strategy to engage them in treatment for psychosis, with an emphasis on compli-ance with antipsychotic medication and the maladaptive effects of substance abuse. For most patients, the problem of substance abuse diminishes after a year of compliance with medication and treatment for addiction. In this setting, the use of long-acting depot antipsychotic preparations is rational. Medication may also be combined with contingency contracting for patients with schizophrenia, making the unsupervised use of disability ben-efits contingent on negative urine toxicology analysis.


Substance-induced disorders (particularly stimulant in-toxication and alcohol or sedative-hypnotic withdrawal) can re-semble generalized anxiety disorder or panic attacks, and thus, as with depression, at least a two week period of abstinence is preferable prior to initiating pharmacotherapy, although again there is room for judgment. Other anxiety disorders, such as social phobia, agoraphobia, PTSD or OCD have distinctive symptoms that do not overlap with symptoms of toxicity or withdrawal. Behavioral approaches are effective for many anxi-ety disorders, and should be considered, first alone and then as a supplement to pharmacotherapy. Antidepressants are effective in the treatment of panic disorder or generalized anxiety dis-order and have less abuse potential than the benzodiazepines. Buspirone may be effective in generalized anxiety disorder, especially at a dose of at least 45 mg/day. If a benzodiazepine is prescribed, clinical opinion supported by experimental evi-dence suggests that oxazepam and chlordiazepoxide are the saf-est alternatives because of their gradual onset of action and a lower risk of euphoria. In general, benzodiazepines should be avoided due to their abuse potential.


Substance abuse occurs frequently in patients with bipo-lar disorder but there is a lack of evidence of the effects of its treatment on substance abuse. Lithium does not appear to have significant interactions with alcohol and cocaine but there is little information about the safety of carbamazepine or valproic acid in pateints with bipolar disorder and substance abuse.


Attention deficithyperactivity disorder (ADHD) occurs more frequently than expected among patients with sub-stance abuse disorders, and high rates of substance abuse occur in children with both ADHD and conduct disorder. It is possible that such patients may preferentially seek stimulants as self-medication of their behavior disorder. The diagnosis of ADHD should be confirmed by evidence of childhood illness and if possible verified by another informant. There is some evidence that methylphenidate may be helpful in such cases and desipramine and bupropion, both of which are used to treat ADHD in children, have also been suggested. Studies are un-der way to improve our understanding of substance abusers with ADHD.


Drug Interactions in Chemical Dependency


Drug interactions in patients with chemical dependency may be pharmacodynamic or pharmacokinetic, and may occur be-tween drugs of abuse or between drugs of abuse and prescribed medications.




The combination of alcohol and cocaine has been associated with increased hepatotoxicity and fatal cardiotoxicity. Alcohol together with opiates or cannabis causes greater sedation and neurologic impairment than any of these agents alone. Acute alcohol intoxication inhibits hepatic enzymes, increasing blood levels of drugs metabolized by this system. By contrast, chronic alcohol use induces hepatic enzymes and lowers blood levels of antipsychotic drugs, tricyclic antidepressants, valproic acid, carbamazepine and certain benzodiazepines. Griseofulvin, metronidazole, chloramphenical and oral hypoglycemic agents cause a mild disulfiram-like reaction in combination with alcohol. Chloral hydrate and alcohol are both metabolized by a pathway dependent on alcohol dehydrogenase; taken simultaneously, competition for this enzyme results in higher blood levels of both agents (this combination is known as a “Mickey Finn”).

Cocaine and Other Stimulants


The combination of cocaine and cannabis is associated with more tachycardia than with either agent alone. Combining heroin and cocaine in a “speedball” more readily produces respiratory de-pression than either alone. The use of cocaine or amphetamine by someone taking a monoamine oxidase inhibitor may result in hypertensive reactions.




Methadone increases blood levels of tricyclic antidepressants and zidovudine. Conversely, methadone levels may be reduced to the point where abstinence occurs by rifampin, phenytoin, bar-biturates and carbamazepine. Meperidine taken during treatment with a monoamine oxidase inhibitor may cause extreme reac-tions ranging from collapse (hypotension and coma) to excitation (hypertension and convulsions).




Smoking cigarettes smoking lowers blood levels of caffeine; caffeine toxicity may be therefore be misinterpreted as nicotine withdrawal in patients who stop smoking. Smoking also lowers blood levels of antipsychotic drugs, tricyclic antidepressants, theophylline and propranolol.




Hallucinogens may act partly via serotonergic mechanisms and it is therefore unsurprising that a serotonin reuptake inhibi-tor reportedly exacerbated hallucinogen-persisting perception disorder (flashbacks) in adolescent LSD users.


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