Drug Treatments for Nicotine Dependence Nicotine resembles other addictive drugs in that it induces

similar addictive behavior patterns (such as inability to control consumption) and similar neuroadaptive changes (e.g., toler- ance). Nicotine intoxication and withdrawal are not associated with the acutely harmful behavior that other drugs of abuse cause but the health consequences of nicotine make it the most important drug of abuse. Withdrawal symptoms associated with nicotine addiction include anxiety, restlessness, diffi- culty concentrating, and irritability. Drug treatment to prevent

248 HANDBOOK OF PSYCHIATRIC DRUGS

relapse in individuals with nicotine addiction must reduce these symptoms and in addition decrease craving for nicotine. This must be achieved in an environment with multiple conditional stimuli for nicotine use, such as the morning cup of coffee.

Nicotine can be delivered safely and its use gradually reduced using nicotine replacement therapy. By contrast with methadone maintenance, nicotine replacement therapy is not an indefinite maintenance treatment but it is worthwhile spec- ulating whether nicotine replacement reduces harm compared with cigarette smoking. Nicotine replacement therapy is currently available as a transdermal patch and polacrilex ’gum’ and both are effective in promoting abstinence.

The FDA recently approved a sustained-release formu- lation of bupropion for the treatment of nicotine dependence. It is as effective as nicotine replacement therapy. The suggested dose is 150 mg twice daily, beginnning two weeks before smoking cessation is attempted. In patients who derive no benefit from nicotine replacement or bupropion alone, a combination of the two therapies has been shown to be safe and more effective than monotherapy.

Many patients who succeed in initiating abstinence from cigarettes will relapse within 3–6 months. Clinicians and patients should not be discouraged by this. The data suggest that most patients who make repeated quit attempts eventually succeed in achieving sustained abstinence.

PHARMACOTHERAPIES FOR SUBSTANCE ABUSERS WITH ADDITIONAL PSYCHIATRIC ILLNESS

There is consistent evidence that patients with psychiatric illness have higher than expected rates of substance abuse, and that patients undergoing treatment for substance dependence have higher than expected rates of psychiatric illness.

In this challenging patient population, clinical experience has confirmed that:

• treatment should be administered by health profes- sionals with expertise in general psychiatry and chemical

dependence • it is unrealistic to insist on abstinence as a condition for treatment

249 • abstinence is not necessary for the safe and effective use of

DRUGS FOR TREATING SUBSTANCE ABUSE DISORDERS

most psychotropic drugs • symptom stability may be needed before a reduction in

substance use is apparent • substance use disorder tends to persist unless it is treated as an illness in itself, regardless of the effective management of other psychopathology

This section summarizes the management of particular psychiatric illnesses complicated by substance use and ends with a summary of important drug interactions in substance use disorders.

Pharmacotherapy for Specific Psychiatric Disorders It is difficult to be definitive about when a substance-induced

mood disorder becomes a major depressive episode. According to most experts, there should be a period of sobriety lasting two weeks before a second diagnosis can be made in a patient presenting with a depressive syndrome. However, clinical trials have shown the benefit of antidepressant medication in patients who are not abstinent to begin with. Thus, there is room for clinical judgment, and, if significant depression persists and the patient cannot achieve abstinence, trials of antidepressant medications can be attempted. In a patient vulnerable to substance abuse relapse, the most worrying effects of antidepressant medication are cardiotoxicity (e.g., arrhythmias), neurotoxicity (e.g., seizures) or death from inten- tional overdose. These concerns are greatest with tricyclic antidepressants and the selective serotonin reuptake inhibitors have a safer pharmacologic profile. Although it is important to discourage individuals from using drugs of abuse, a significant number of people taking an antidepressant use alcohol and other potential drugs of abuse in moderation without ill effects. There seems to be little abuse potential with antidepressants though abuse of amitriptyline for its sedative effects and, more recently, fluoxetine for its stimulant effects, has been reported.

Substance abuse or dependence are frequent complica- tions of schizophrenia; conversely, the psychotic symptoms that occur during drug intoxication and withdrawal complicate the diagnosis of schizophrenia. These patients need a particularly

250 HANDBOOK OF PSYCHIATRIC DRUGS

high degree of patience and sophisticated psychiatry services. Long-term follow-up (more than one year) of patients with schizophrenia and substance abuse suggests the need for ener- getic engagement in treatment for psychosis with an emphasis on compliance with antipsychotic medication and the maladap- tive effects of substance misuse. The problem of substance abuse declines for most patients after a year of medication compliance and treatment for addiction. Long-acting depot antipsychotics are a rational component of such a strategy. A combination of medication and contingency contracting has also been used for patients with schizophrenia, in which unsu- pervised use of disability benefits is contingent on negative urine toxicology.

Substance-induced disorders (particularly stimulant intoxication and alcohol or sedative–hypnotic withdrawal) can resemble 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 anxiety disorders and should be considered, first alone and then as a supplement to pharmacotherapy. Antide- pressants are effective for panic disorder or generalized anxiety disorder and have less abuse potential than the benzodiazepines. Buspirone may be beneficial for generalized anxiety disorder at a dose of at least 45 mg/day. If a benzodiazepine is still preferred, expert opinion (supported by some experi- mental evidence) suggests that the safest agents are oxazepam and chlordiazepoxide because their onset of action is more gradual and they have a lesser tendency to produce euphoria. In general, however, benzodiazepines should be avoided owing to their abuse potential.

Substance abuse and bipolar disorder (particularly in the manic phase) are frequently comorbid disorders but there is little information about the effects of treatments for bipolar disorder on substance abuse. Research in the treatment of alcohol and cocaine dependence suggests that concurrent use of lithium is relatively safe with regard to drug interactions but

251 little is known about the risk of interactions between carba-

DRUGS FOR TREATING SUBSTANCE ABUSE DISORDERS

mazepine and valproate and drugs of abuse in patients with bipolar disorder.

Follow-up of children with attention deficit–hyperactivity disorder (ADHD) and conduct disorder has revealed high rates of substance abuse, and ADHD may be over-represented in substance abuse treatment settings. It is possible that patients with ADHD may seek stimulants for self-medication. The diagnosis of ADHD requires evidence of illness during childhood, preferably with verification from another person. These patients have benefited from methylphenidate, according to some reports. Desipramine and bupropion have been used successfully in treating children with ADHD and both have been advocated in patients with comorbid substance abuse.

Drug Interactions in Chemical Dependency Drug interactions in patients with chemical dependency may

be pharmacodynamic or pharmacokinetic, and may occur between drugs of abuse or between drugs of abuse and prescribed medications.

ALCOHOL The combination of alcohol and cocaine has been associated with fatal cardiac events and increased hepatoxicity. Alcohol in combination with an opiate or cannabis cause greater sedation and greater neurologic impairment than when used alone. Acute alcohol intoxication is associated with inhibi- tion of hepatic enzymes and may increase blood levels of concurrent medication. Conversely, chronic alcohol use causes enzyme induction, leading to lower blood levels of antipsychotic drugs, antidepressants, valproic acid, carbamazepine, and some benzodiazepines. Griseofulvin, metronidazole, chlo- ramphenical and oral hypoglycemic agents may cause mild disulfiram-like reactions with alcohol. Alcohol and chloral hydrate compete for alcohol dehydrogenase; concurrent inges- tion leads to higher blood levels of both and increased intoxication (this combination is known as a ‘Mickey Finn’).

252 HANDBOOK OF PSYCHIATRIC DRUGS COCAINE AND OTHER STIMULANTS

The risk of tachycardia is greater with a combination of cocaine and cannabis than with either drug alone. A ‘speedball’ (heroin and cocaine) more easily produces respiratory depression than the single drugs. Taking cocaine or amphetamine during or shortly after treatment with a monoamine oxidase inhibitor can lead to hypertensive reactions.

OPIATES Methadone increases blood levels of concurrently taken antidepressants and zidovudine. Conversely, blood levels of methadone may be reduced to the point where abstinence symptoms occur by concurrent use of rifampin, phenytoin, barbiturates, and carbamazepine. The combination of meperi- dine and a monoamine oxidase inhibitor may cause extreme reactions ranging from collapse (hypotension and coma) to excitation (hypertension and convulsions).

NICOTINE Cigarette smoking reduces blood levels of caffeine; patients who stop smoking may therefore experience caffeine toxicity and this could be mistaken for nicotine withdrawal. Smoking also reduces blood levels of antipsychotic drugs, tricyclic antidepressants, theophyline, and propranolol.

HALLUCINOGENS

A serotonin reuptake inhibitor reportedly exacerbated hallucinogen-persisting perception disorder (flashbacks) in adolescents with a history of LSD use. This is not surprising given the role of serotonergic mechanisms in hallucinogenic drug effects.

ADDITIONAL READING 1. Substance Abuse: A Comprehensive Textbook (4th Edition).

Edited by Lowinson JH, Ruiz P, Millman RB, Langrod JG. Lippincott Williams and Wilkins, Philadelphia, 2005

2. Principles of Addiction Medicine (3rd Edition). Edited by Graham AW, Schultz TK, Mayo-Smith MF, Ries RD, Wilford BB. American Society of Addiction Medicine, Inc., Chevy Chase, Maryland, 2003

253 3. Textbook of Substance Abuse Treatment (3rd Edition). Edited by

DRUGS FOR TREATING SUBSTANCE ABUSE DISORDERS

Galanter M, Kleber HD. American Psychiatric Publishing, Inc., Washington, D.C., 2004

4. Clinical Textbook of Addictive Disorders (3rd Edition). Edited by Frances RJ, Miller SI, Mack AH. The Guilford Press, New York, 2005

5. International Handbook of Alcohol Dependence and Problems. Edited by Heather N, Peters T, Stockwell T. John Wiley and Sons Ltd., Chichester, UK, 2001

Drug Treatments for Nicotine Dependence Nicotine resembles other addictive drugs in that it induces