• December 12, 2007, Carbamazepine: The U.S. Food and Drug Administration (FDA) has provided recommendations for screening that should be performed on specific patient populations before starting treatment with carbamazepine.
• September 17, 2007, Haloperidol (Haldol): Johnson and Johnson and the U.S. Food and Drug Administration (FDA) informed healthcare professionals that the WARNINGS section of the prescribing information for haloperidol has been revised to include a new Cardiovascular subsection.
• May 2, 2007, Antidepressant drugs: Update to the existing black box warning on the prescribing information on all antidepressant medications to include warnings about the increased risks of suicidal thinking and behavior in young adults ages 18 to 24 years old during the first one to two months of treatment.

Follow-up for hepatitis B and C should be arranged for after discharge from the detoxification setting. Vaccination is recommended for hepatitis A and B in the patient with hepatitis C. The vaccination schedule is over a 6-month period, so it needs to be done after the detoxification program. If significant liver disease is present, use of shorter-acting medication with less liver metabolism should be considered. For more on infectious disease and substance abuse, see TIP 6, Screening for Infectious Diseases Among Substance Abusers.

Endocarditis

Endocarditis is caused by the introduction of various bacterial species into the vascular system when the protective defense mechanisms of the skin are bypassed through injection. The patient frequently will present with fever, cardiac murmur, anemia, enlargement of the spleen, petechiae, and peripheral embolic disease. The course can be subtle and indolent to fulminant, and if untreated can lead to a poor prognosis. In the patient who uses drugs intravenously, the tricuspid valve is affected in 70 percent of cases, followed by effects on the aortic valve and the mitral valve. Seventy-five percent of all cases are caused by Staphylococcus aureus and up to 15 percent are caused by gram negative aerobic bacilli.

Endocarditis always should be suspected in the febrile patient who uses intravenous drugs. Patients who use drugs intravenously are 300 times more likely to die suddenly from infectious endocarditis than patients who use drugs nonintravenously. Patients who use cocaine intravenously may have a higher rate of endocarditis as a result of more frequent injections and the reduced need to solubilize cocaine solutions with heat.

Bacterial Pneumonia

Bacterial pneumonia can result from immune system dysfunction, interference with normal respiratory defense mechanisms (from alcohol or smoked drugs), direct toxicity, or aspiration.

The treating physician should be aware that the usual pathogens found in community-acquired pneumonia (i.e., Streptococcus pneumoniae) may not be the causative agent in pneumonias seen in patients dependent on alcohol. Haemophilus influenzae, Klebsiella pneumoniae, and other gram-negative microorganisms must be suspected and treatment given until definitive culture results are reported. Among patients who use parenteral drugs, pneumonia is the most common reason for admission to the hospital, accounting for 38 percent of all hospitalizations in this population.

Special Considerations

Careful use of respiratory depressants is recommended. Indications for hospitalization of the patient with pneumonia include the following:

• Old age
• Dehydration
• Vomiting and inability to take in oral fluids and medications
• Multilobar disease
• Low white blood cell count
• Respiratory acidosis
• pO2 less than 55 mm Hg
• Significant concomitant diseases
• HIV

Tuberculosis (TB)

Tuberculosis is caused by acid-fast rod (Mycobacterium tuberculosis). Transmission is by droplets spread through the air. The infected patient presents with complaints of cough (most common finding), bloody sputum, chest pain, fever, and weight loss. Recent immigrants from countries where TB is prevalent, socioeconomically disadvantaged populations, homeless persons, people who use illicit drugs, incarcerated people, and people who live in areas where infection with HIV is prevalent, are at increased risk for this disease and should be tested. Furthermore, new strains of multidrug-resistant TB are appearing, especially among the homeless population.

TB is endemic in many areas of the world (Asia, Africa, and South and Central America). As a public health concern, testing all patients is of the utmost importance, even more so for patients from regions where TB is endemic. It is important to remember that immunocompromised patients may not react to the skin tests (anergy). Diagnosis is made with tuberculin skin testing, sputum smears and cultures, and radiographic findings. For more information on dealing with tuberculosis in detoxification and treatment settings see TIP 18, The Tuberculosis Epidemic: Legal and Ethical Issues for Alcohol and Other Drug Abuse Treatment Providers.

Skin Infections

Skin infections frequently are seen as a result of the intravenous administration of drugs. Staphylococcus aureus and Streptococcus pyogenes are frequently the infectious agents. The patient presents with tenderness, swelling, pain, erythema, and warmth in the injection area. The type and route of antibiotic is determined by the infecting organism and the extent and severity of the infection. Clinicians should remember that injection sites can be found virtually any place on the body where there is access to the venous system.

Patients who use drugs intravenously, patients with peripheral vascular disease, and patients with diabetes (particularly with infections of the feet) should all be evaluated carefully for skin disease.

Sexually Transmitted Diseases

Sexually transmitted diseases can be seen in the form of urethritis, vaginitis, cervicitis, and genital lesions. These disorders are caused by a variety of microorganisms, and a complete history and physical that includes examination of the genitalia is indicated in all patients. The clinical picture and cultures frequently can guide the treatment protocols. Patients who use drugs intravenously occasionally display a false-positive serologic test for syphilis, possibly due to a nonspecific reaction to repeated exposure of injected antigens.

HIV/AIDS

HIV/acquired immune deficiency syndrome (AIDS) is a serious and prevalent medical condition among persons with substance use disorders, especially those who inject drugs and may share needles with other users. Patients with AIDS can present with a spectrum of complaints and illnesses ranging from an asymptomatic history to complaints of fever, enlargement of the lymph nodes, difficulty swallowing, diarrhea, weight loss, skin lesions, shortness of breath (due to Pneumocystis carinii pneumonia), headaches (due to Toxoplasma gondii), seizures, and dementia. As a rule of thumb, no complaint in the patient infected with HIV should be dismissed as irrelevant.

Gay men and patients who use drugs intravenously may be at higher risk for HIV/AIDS than other groups; thus, testing or referral for testing should be done and appropriate counseling offered. All such patients should be tested for HIV/AIDS or referred for testing. Some States, such as Colorado, require that a risk assessment be administered to all clients and that clients be advised of their risk and referred for testing if they are at risk for HIV/AIDS. Patients who decline HIV testing still should be educated about the risk and prevention.

Due to increased virulence of syphilis in patients who are HIV positive, as well as increased resistance to the treatments indicated in the usual treatment protocols, all such patients should be tested for syphilis and all patients who test positive for syphilis should be sent for HIV testing.

Special Considerations

If methadone is being used in withdrawal protocols, or maintenance is being continued, the clinician should be aware that certain HIV medications can cause an increased metabolism of methadone:

• Efavirenz (Sustiva)
• Nevirapine (Viramune)
• Lopinavir/ritonavir (Kaletra)
• Rifampin (a drug to prevent mycobacterium avium complex, a serious bacterial infection, in HIV-positive clients)
• Amprenavir (Agenerase)
• Abacavir
• Ritonavir

TIP 37, Substance Abuse Treatment for Persons With HIV/AIDS provides further information about substance abuse treatment for patients with HIV/AIDS.

Other Conditions

Cancer

Cancer occurrence is increased in people with substance use disorders due to the carcinogenicity of the drugs used. Cigarette smoking is linked to lung, larynx, oral cavity, esophagus, stomach, bladder, and pancreatic cancer. Heavy alcohol consumption is associated with an increased incidence of oral, pharyngeal, esophageal, laryngeal, respiratory tract, and breast cancer. Synergism is seen with alcohol and smoking being associated with even higher risks of cancer. A history of weight loss could suggest many chronic diseases, though cancer should be considered in the differential. There may be an increase in head and neck cancers in persons with heavy cannabis use. Liver cancer may be seen in patients with hepatitis C and those using anabolic steroids. There is a particular interrelationship among alcohol intake, hepatitis C, and hepatocellular carcinoma.

Diabetes

Patients who use drugs intravenously may experience infections that affect diabetic control, though any infection in any detoxification patient needs to be addressed both from an infectious disease and diabetic viewpoint.

Special Considerations

Several medications can lead to impaired glucose tolerance and an elevated serum glucose. Some examples include

• Thiazide diuretics
• Clonidine
• Glucocorticoids
• Haloperidol
• Lithium carbonate
• Phenothiazines
• Tricyclic antidepressants
• Indomethacin
• Olanzapine
• Risperdal

Antidiabetic agents in concert with alcohol may produce hypoglycemia and lactic acidosis. Diabetes mellitus also is seen in patients who present with new-onset hyperglycemia (elevated glucose) or with a history of diabetes and poor control.

Acute Trauma/Fractures

Acute trauma/fractures can be seen in any patient with a substance use disorder due to an altered level of consciousness or impaired gait when intoxicated. Patients with substance use disorders appear to be particularly prone to accidents of all kinds, with a spectrum of complications from head trauma to falls with fractures. Chronic pain frequently is seen in patients as a result of trauma (treated or untreated), poor health maintenance, or an inability to deal with pain without drug use. Chronic pain treatment and the issues of opioid use have to be considered for each patient on an individual basis.

The surgeon should consider drug withdrawal in the differential diagnosis of any physical or neurologic symptoms or signs that emerge during the perioperative period. There is a two- to threefold increase in postoperative morbidity in patients with alcohol use disorders, the most frequent complications being infections, bleeding, cardiopulmonary insufficiency, and withdrawal complications.

Special Considerations

Opioids may be used to control pain in the initial period of trauma. Detoxification protocols should be started prior to anticipated surgery and continued throughout the perioperative period. Pain that causes an increased heart rate, as well as postoperative temperature elevation, may impact the detoxification parameters.

Due to tolerance to opioids, the daily methadone dose in a methadone-maintained individual will not serve as an analgesic for pain relief from surgical or other illnesses. Full therapeutic doses of analgesic drugs should be given to methadone-maintained patients who have co-occurring painful conditions.

Since most medications for pain management are drugs with a high abuse potential, programs may need to alter their policies regarding the use of such drugs. Pain patients do not require detoxification from prescribed medications unless they meet the criteria for opioid abuse or dependence described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Treatments for pain include physical therapy, transcutaneous electrical nerve stimulation, and therapeutic heat and cold. Trials of nonsteroidal anti-inflammatory agents or nerve block should be considered prior to the use of highly addictive and abusable medications.

The use of acetaminophen in the patient with an alcohol use disorder always has been questioned, especially if there is evidence of liver disease. However, a review article of the medical literature showed that repeated ingestion of a therapeutic dose of acetaminophen over 48 hours by patients with severe alcoholism did not produce an increase in hepatic aminotransferase enzyme levels or any clinical manifestations as compared to a placebo group.

Treatment of Co-Occurring Psychiatric Conditions

Pharmacological agents can be used as indicated for co-occurring psychiatric conditions in patients with substance use disorders. Incidence of the co-occurrence of psychiatric conditions and substance use disorders is high; moreover, there is a higher rate of psychiatric conditions in patients dependent on alcohol than that found in the general population.

Comorbidity of substance use and co-occurring mental disorders serves to complicate diagnosis and treatment for patients. It is difficult to accurately access underlying psychopathology in a person undergoing detoxification. The effects of drug toxicity and withdrawal often can mimic psychiatric disorders. For this reason, it may be best to conduct psychiatric evaluations after several weeks of abstinence; however, this should be weighed against the time an individual has been in detoxification and what treatment plan is set up for him. Some patients also present to detoxification while taking medications to treat underlying psychiatric disorders, such as depression and anxiety. The risk of not treating a severe comorbid psychiatric disorder predisposes the patient to relapse; the decision needs to be weighed against the risk of prescribing medications when the clinician is not entirely certain that a comorbid condition exists. If a period of recent extended abstinence exists, the patient's mental condition when abstinent can be better evaluated.

Although it is the philosophy of some physicians to discontinue all psychiatric medications upon entering a detoxification program, this course of action is not always in the best interest of the patient. Abrupt cessation of psychotherapeutic medications may cause withdrawal symptoms or the re-emergence of the psychiatric disorder. As a general rule, therapeutic doses of medications should be continued through any withdrawal if the patient has been taking the medication as prescribed. Decisions about discontinuing medications should be deferred until after the individual has completed detoxification. If, however, the patient has been abusing a medication or the psychiatric symptoms were clearly caused by substance abuse, then the rationale for discontinuing the medication is strengthened. Finally, practitioners should consider withholding medications that lower the seizure threshold (e.g., bupropion or conventional antipsychotics) during the acute alcohol withdrawal period, or at a minimum prescribing a loading dose or scheduled taper of benzodiazepine.

During detoxification, some patients decompensate and lapse into psychosis, depression, or severe anxiety. In such cases, careful observation of the withdrawal medication regimen is of paramount importance. If the decompensation is a result of inadequate dosing with withdrawal medication, the appropriate response is to increase the dose of medication. If it appears that the withdrawal medication is adequate, other medications may be needed. Before choosing such an alternative, it is important to take into account additional considerations, such as the side effects of the added medication and the possibility of interaction with the withdrawal medication.

A patient with psychosis may need to take neuroleptics. Medications that have a minimal effect on the seizure threshold are recommended, particularly if the patient is being withdrawn from alcohol or benzodiazepines. Small, frequent doses of Haldol, such as 1 mg every 2 hours, may be used until the patient's symptoms of psychosis begin to disappear. The case for emergency use of antidepressants is weaker than for other psychiatric medications because of the 2- to 3-week lag time between initiation of medication and therapeutic response. After detoxification, the patient's need for medication should be reassessed. A trial without medications sometimes is the best way to assess the patient's need for the medication; however, it may not be the best practice or in the best interest of the patient, particularly for those with a serious mental illness. For more information on working with patients with co-occurring substance use and mental disorders, see the National Guideline Clearinghouse (NGC) summary of the Substance Abuse and Mental Health Services Administration (SAMHSA) TIP 42, Substance Abuse Treatment for Persons With Co-Occurring Disorders.

Treatment for Co-Occurring Conditions

The treatment of substance use disorders can be difficult without adequate treatment of any co-occurring mental disorders. For instance, a patient with schizophrenia who is hallucinating and delusional, but who also abuses substances, cannot participate in substance abuse treatment without adequate control over the psychosis. Likewise, patients with mania who are euphoric and delusional, patients who are depressed, or patients with agoraphobia who also have a substance use disorder, will have difficulty cooperating with substance abuse treatment. Treatment of the substance use disorder is necessary to improve the course of both the substance abuse and co-occurring mental disorder. Psychotherapy should serve as one aspect of rehabilitation, initially focused around relapse prevention. Highly effective treatment programs may include a combination of therapeutic techniques. Programs should be long-term and approach recovery in stages. One study suggests that treatment for co-occurring substance use and other mental disorders include skill building, illness management, cultural sensitivity, and support to patients for the pursuit of practical goals.

Limitations of Pharmacological Agents in Persons with Substance Dependence

Pharmacologic agents have limitations in the population of persons with substance use disorders. Medications may impair cognition and blunt feelings, sometimes subtly. Clinicians treating substance use disorders advocate that clients need clear thinking and access to emotions in order to make fundamental changes in themselves. A person recovering from a substance use disorder must take an active part in changing attitudes and abandoning a long-held belief that alcohol or other drugs can "treat" life problems and uncomfortable psychological states. Although these are potential risks, the intent of pharmacotherapy is to enhance a person's ability to sustain abstinence and benefit fully from concurrent psychosocial interventions and treatments. Still, many psychiatric disorders, if untreated, result in mood, anxiety, or thought disorders that prevent or retard the behavioral changes necessary to recover from substance use disorders.

Risks versus benefits of pharmacological agents need to be considered carefully. Untreated anxiety, mood, or thought disorders can be powerful relapse triggers, especially for people with a long-standing pattern of relying on alcohol or other drugs to manage their symptoms. In many instances, the benefits and reduced relapse risk that appropriate pharmacotherapy can provide far outweighs the risk of taking medications. Some clinicians believe that the "no pain, no gain" approach has far greater risk of interfering with recovery than of promoting it. Symptoms such as anxiety and depression in persons recovering from substance use disorders might be vital to recovery, and pharmacotherapy to treat such symptoms needs to be considered carefully in this context. Clinically, anxiety and depression can provide the motivation to change when the patient otherwise has little awareness of the need to alter behavior.

Standard of Care for Co-Occurring Psychiatric Conditions

After detoxification and stabilization with pharmacologic agents, the current treatment of choice for substance use disorders is nonpharmacologic. Further, several studies have shown that treating substance use disorders with abstinence alone results in improvement of the psychiatric syndromes associated with the substance use. Severe syndromes induced by alcohol that may otherwise meet criteria for major depressive and anxiety disorders are best classified as substance-induced disorders if they resolve within days to weeks with abstinence. Likewise, manic syndromes induced by cocaine resolve within hours to days, and schizophrenia-like syndromes (e.g., hallucinations and delusions) induced by cocaine and phencyclidine (PCP) often resolve within days to weeks with abstinence.

Further studies are needed to confirm the clinical experience that psychiatric symptoms (including anxiety, depression, and personality disorders) respond to specific treatment of the addiction. For example, cognitive–behavioral techniques employed in the 12-Step treatment approach have been effective in the management of anxiety and depression associated with addiction. Although challenging, treatment of both addiction and co-occurring psychiatric conditions has proven cost-effective in some studies.

Psychotropics for Co-Occurring Psychiatric Conditions

General Aspects

Because alcohol and other drugs can induce almost any psychiatric symptom or sign or mimic any psychiatric disorder, their effects always must be considered before a co-occurring condition diagnosis is established or treated.

With an understanding of the interactions between substance use and other mental disorders, a rational approach can be applied to the use of pharmacologic therapies in co-occurring conditions. The use of medications for psychiatric symptoms should begin only after the knowledge of the natural history of the addictive disorder and other psychiatric disorders is clarified. Further, it is important to be able to identify the respective roles of substance use and other mental disorders in the generation of psychiatric symptoms.

Generally, substance-induced psychiatric symptoms resolve within days to weeks of abstinence. In many studies, the prevalence rates for anxiety and affective disorders in persons dependent on alcohol were not greater than those for persons not dependent on alcohol.

A retrospective history of psychiatric symptoms often can lead to an inflated diagnosis of these conditions because of rationalizations regarding drinking and drug use by the individual. Typically, psychiatric symptoms are emphasized by both the patient and the psychiatric examiner.

Longitudinal observation frequently clarifies the role of alcohol and other drugs in the production of anxiety, affective, psychotic, or personality symptoms, particularly if objective criteria are relied on in addition to the subjective report of the person who is addicted. Also, specific treatment of substance use disorders can result in improvement of mood, psychotic behavior, and personality disturbances if related to the alcohol or other drug use. Mood lability and personality states can be a manifestation of substance use disorders, and treatment of the addictive disorder can lead to stabilization of these psychiatric symptoms.

Furthermore, treatment plans and efficacy may rely on the gender of the patient. Women with a substance use disorder appear to have higher rates of co-occurring mental disorders, such as depression and anxiety, as well as higher rates of physical and sexual abuse, panic and phobia disorders, posttraumatic stress disorder, victimization, and eating disorders. Deficits in the management of mood disturbances may be self-medicated through alcohol consumption in females. It has been proposed that the outcomes of substance abuse in women are different when compared to those of men. For these reasons, the efficacy of treatment for substance use disorders needs to be assessed independently for both genders.

Anxiety Disorders

General Approach

Prevalence rates for the co-occurrence of anxiety and substance use disorders in the general population range from 5 to 20 percent in epidemiologic and clinical studies.

Some antianxiety agents can oversedate and dull the individual's reaction to internal and external influences. Because anxiety in recovery can be critically important for emotional growth, the individual will feel a certain amount of anxiety to motivate change in behavior, attitudes, and emotions. (The expression "emotional growth" is related to the anxiety or discomfort a recovering individual feels while undergoing the process of change to reach a more mature state.) It is important for the clinician to distinguish between anxiety that can promote growth and anxiety that can impair a person's ability to make change. Adapting behavior in response to anxiety or other emotion requires coping skills that may not be available to persons in early recovery. A fully symptomatic anxiety disorder may significantly limit a person's capacity to learn nonpharmacological coping strategies. Medications with minimal addiction potential can be helpful and in some cases necessary if patients are to make progress in their recovery.

Depressants (e.g., alcohol) can produce anxiety during withdrawal, and stimulants (e.g., cocaine) can produce anxiety during intoxication. Because people with substance use disorders are in a relatively constant state of withdrawal (it is impossible to maintain a constant blood level), they regularly experience anxiety as the result of pharmacological withdrawal from dependence. As the substance abuse becomes more chronic, the anxiety produced by withdrawal from pharmacologic dependence can become increasingly severe. Relapse and/or periods of abstinence (sometimes prolonged--for weeks or months) should be considered (confirm abstinence with laboratory drug testing, if necessary) before the effects of depressant or stimulant drugs in inducing anxiety can be ruled out. It can take weeks or months for these effects to subside completely, although a period of only a few days to weeks often is sufficient in clinical practice.

Treatment is indicated when the anxiety persists after adequate effort in a substance abuse treatment program, or when the clinician suspects that anxiety is preventing the patient from participating in treatment. A thorough evaluation to assess whether the individual is abstinent, involved in continuing treatment, and/or attending self-help meetings usually is necessary before a diagnosis of a co-occurring psychiatric condition can be definitely established. After such an evaluation, treatment of the anxiety disorder can proceed separately from similar symptoms arising from the addictive disorder.

Pharmacologic Therapies

The ideal medication works against abnormal anxiety but not against the "normal" anxiety needed for recovery. Some of the physical symptoms of anxiety include sweating, tremors, palpitations, muscle tension, and increased urination. Psychological symptoms include nervousness, feelings of dread or impending doom, unpleasant tenseness, and many more.

The most common agents used in anxiety disorders are benzodiazepines and antidepressants. The benzodiazepines most frequently used are alprazolam and lorazepam. Diazepam and clonazepam are used less often. Because the benzodiazepines can cause significant problems in patients who are addicted as well as in patients who are not addicted, they generally are not recommended for people with substance use disorders or for long-term treatment of anxiety or depressive disorders.

Antidepressants may be considered sooner if depression is a known pre-existing condition or historical experience and collateral information suggests a comorbid depression. Again the risk of treating prematurely needs to be weighed against the risk of not treating a condition that may prevent recovery from a substance use disorder. Antidepressants such as imipramine and nortriptyline and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) have a low addiction potential and can be used with relative safety. They differ in their tendency to produce sedation and anxiety and have a withdrawal syndrome of their own. Because of its anticholinergic properties, imipramine is more sedating, but nortriptyline and the SSRIs can produce anxiousness in some individuals and sedation in others. Not all individuals react the same way to these medications.

When medications are used, a specific target symptom should be the focus. Also, medications should be tried in time-limited intervals, such as weeks to months. A "drug holiday" (i.e., a brief period where the patient stops taking medications) should then be attempted to see if the medication is still necessary.

The patient should be instructed that the medications will not "cure" the addiction, that treatment of anxiety will not control the addiction, and that treatment of the addiction will not necessarily ameliorate the anxiety disorder. In essence, the substance use disorder must be treated independently of the anxiety disorder and vice versa.

Depressive Disorders

General Approach

Prevalence rates for the co-occurrence of depressive and addictive disorders range from 5 to 25 percent in epidemiologic and clinical studies. Depressive disorders include major depressive and dysthymic disorders, which can occur independently with addictive disorders, or similar depressive symptoms can be induced by substance use disorders. Major depressive disorder is more common in older individuals and in women and can be difficult to distinguish from substance-induced depression.

Depression can be viewed as protective and can be associated with "healing" in many conditions involving emotions. For example, a grief reaction is an expected experience after loss, with depression an essential emotion in this process. Recovery from a substance use disorder has been compared to a grief reaction because of losses (e.g., of the substance or relationships based on substance use) suffered by the patient with an addictive disorder. Likewise, and analogous to the role of anxiety, depression also is a part of the healing process that the patient with a substance use disorder experiences during recovery.

Depressant drugs (e.g., alcohol) can produce depression during intoxication which often resolves following abstinence. A survey of 69 adults with alcohol use disorders showed a strong correlation between the reduction in cravings for alcohol over 2 weeks of abstinence and the lifting of depressive mood. The patients' cravings were assessed with the Obsessive-Compulsive Drinking Scale (OCDS) and their depressive symptoms measured with the Self-rating Depressive Scale (SDS). Between day 1 and day 14, their cravings score dropped nearly a third, while the scores for severity of depression fell by about one fourth. The correlation between the reduction in cravings and the lifting of depression persisted after controlling for sex, age, duration and extent of alcohol abuse, and the amount of clomethiazole administered.

Stimulant drugs (e.g., cocaine) can produce depression during withdrawal. These effects may be prolonged with certain drugs that linger in the body (i.e., are stored in fat), such as cannabis and benzodiazepines. These drugs can produce depression or anxiety that is indistinguishable from other psychiatric causes of depression. Therefore, they must be considered causative whenever depression is present, and the possibility of addiction needs to be assessed when these drugs are identified. While depression may persist for weeks or months, it often resolves within days with abstinence from these drugs.

Pharmacologic Therapies

The use of medication is recommended if the depression persists beyond a few weeks of drug withdrawal or arises during confirmed abstinence (laboratory drug testing may be necessary to confirm abstinence). The risk of suppressing normal depressive processes during recovery versus the benefit from suppressing depression that is interfering with function should be weighed, as is the case with anxiety disorders.

Antidepressants are the main treatment for depression. The target symptoms are a sad mood, tearfulness, appetite and sleep disturbances, and other neurovegetative symptoms. Depression can be found in many conditions, including a variety of psychiatric and medical conditions. SSRIs are the drug of choice for many physicians treating depressed patients with substance use disorders. Although some are costly, they provide adequate treatment of depression with fewer side effects than other medications commonly used.

Depressive disorders are thought to have a significant biological component, including deficiencies in such central nervous system neurotransmitters as serotonin, norepinephrine, and dopamine. Interestingly, these neurotransmitters are also affected by substances of abuse. These agents are thought to act by increasing the activity of these neurotransmitters, ultimately alleviating depression and stabilizing mood.

Bipolar Disorders

General Approach

Prevalence rates for the co-occurrence of bipolar and addictive disorders range from 30 to 60 percent in epidemiologic and clinical studies.

Mania is a condition associated with elevated mood, grandiosity, hyperactive behavior, poor judgment, and lack of insight. The patient with mania will show excess such as spending sprees, sexual promiscuity, intrusiveness, and abnormal alcohol and drug use. A manic episode can follow, precede, or alternate with depressive moods.

Bipolar disorder may be complicated by the influence of substances. The manic state can be produced by stimulants (e.g., cocaine) during intoxication and from depressants (e.g., alcohol) during withdrawal. A period of confirmed abstinence usually is necessary before mood-stabilizing drugs are started. Generally, a period of a week or two may be required for the role of drugs in inducing manic symptoms to be properly assessed.

Pharmacologic Therapies

Mood stabilizers control bipolar disorders in patients with or without co-occurring substance use disorder. These medications can control either the manic or depressed phase, or both.

Manic episodes can occur cyclically, alternatively, and concurrently with depressive episodes. One theory of the pathogenesis of bipolar disorder involves the neurotransmitter norepinephrine (i.e., excessive in mania and deficient in depression).

Lithium is a natural salt, available in the carbonate form and slow release preparations. Its exact mechanism of action is unknown, but it can be effective in reducing or preventing the recurrence of manic and depressive episodes. Lithium carbonate must be taken daily in doses of 600 to 2,400 mg to achieve plasma levels in the 0.5 to 1.5-m equiv/L range. It should be noted that studies have shown that lithium has no conclusively positive effect on rates of abstinence in either depressed or nondepressed patients.

Anticonvulsant mood stabilizers, such as divalproex sodium and carbamazepine, can be effective in controlling mania and, some evidence suggests, in co-occurring addictive conditions as well. Carbamazepine is known to be as effective as some benzodiazepines in inpatient treatment of alcohol withdrawal and, because of its anticonvulsant properties, it may be a good choice for treating those patients at high risk of withdrawal seizures. One theoretical explanation for the mechanism of action for carbamazepine involves suppression of mood centers in the limbic system that act like seizure foci. In this context, a "kindling" model has been proposed for both mood and addictive disorders.

Psychotic Disorders

General Approach

Prevalence rates for co-occurrence of schizophrenic and addictive disorders range from 40 to 80 percent in epidemiologic and clinical studies.

Schizophrenia is a chronic illness characterized by bizarre thinking and behavior. Hallucinations and delusions are "positive" symptoms of the psychotic process, while symptoms such as social withdrawal and poverty of emotions are "negative" symptoms (or deficit syndrome). Conventional neuroleptics are more effective for positive symptoms, whereas behavioral, group, and individual psychotherapy are more effective for negative symptoms. New agents such as clozapine and risperidone may be more effective in treating both the positive and negative symptoms.

Psychosis can be caused by stimulant drug use during intoxication and depressant drug/alcohol use during withdrawal. A period of weeks or months may be necessary to assess the effects of substances of abuse, but as with anxiety, depression, or mania, medications can be started at almost any time as the psychosis is persistent and waiting is not possible. Moreover, the greater the number of psychiatric admissions, the greater the probability of a chronic mental disorder associated with the co-occurring psychiatric disorder.

High- or moderate-potency neuroleptics (e.g., haloperidol or atypical agents) generally are the agents of choice in the treatment of schizophrenia. The clinical potency correlates with the drug's ability to block the action of the neurotransmitter dopamine at its postsynaptic receptor sites.

Adverse Effects

Antianxiety Agents

While benzodiazepines are useful in the short term, their efficacy wanes with long-term use, probably because of the development of pharmacologic tolerance and dependence. It should be noted that benzodiazepines can be addicting, particularly in those already addicted to other substances.

Antipsychotic Agents

Antipsychotics can produce sedation and hypotension (at times causing lightheadedness in some individuals), particularly with postural changes. Conventional neuroleptics produce acute extrapyramidal reactions, which include pseudoparkinsonism, dystonia, and akathisia. Dystonia usually responds to treatment with anticholinergic drugs such as benztropine or diphenhydramine. Akathisia is the subjective feeling of anxiety and tension, causing the patient to feel compelled to move about restlessly. This symptom usually requires beta blocker, as a decrease in the antipsychotic dose does not have the desired effect. Alternatively, switching to risperidone may accomplish the intended effect while avoiding intolerable neurologic syndromes.

Antidepressants

Antidepressants, particularly the tricyclics, can produce sedation, hypotension, syncope, and other anticholinergic effects. The SSRIs can produce anxiousness, sedation, insomnia, and gastrointestinal upset. A withdrawal syndrome also has been reported with most antidepressant medications.

The SSRIs are preferred in patients with addiction and co-occurring psychiatric conditions because of their reduced side effect profile and low risk of dangerous drug interactions; for example, there are no anticholinergic effects on the senses and no risk of lethal effects from overdose.

Cognitive State in Recovery

A person recovering from a substance use disorder must have a clear mind and a stable mood. Medications have a tendency, sometimes subtly and other times obviously, to dull the senses and thinking and blunt or disrupt the emotions. People with substance use disorders must eventually change and control feelings to remain abstinent and also to comply with psychiatric management. The ability of a person with a substance use disorder to use the 12 steps of Alcoholics Anonymous (AA) and to accept psychiatric advice will depend on clear thinking and emotional balance, which is stressed as central to the recovery process in AA. In other cases--such as patients with traumatic brain injuries--treatment venues should be adaptable to their cognitive abilities.

Accordingly, the use of medications should be conservative, taking into consideration the pros and cons of their expected positive and negative effects. Unfortunately, few psychiatric medications are totally free of mood-altering properties. However, the cognitive state of individuals who have a serious mental illness often is more distorted when not medicated appropriately. The very nature of their illness is a disruption to their cognitive processes.

Dosing

Because of inherent susceptibility to drug effects by people with substance use disorders, it is important to use the lowest effective doses possible. Also, the intervals for administration should be selected to reduce effects on cognition and feelings.

For information about availability, see the "Availability of Companion Documents" and "Patient Resources" fields below.

Electronic copies: Available from the National Clearinghouse for Alcohol and Drug Information (NCADI) Web site.

Print copies: Available from the National Clearinghouse for Alcohol and Drug Information (NCADI), P.O. Box 2345, Rockville, MD 20852. Publications may be ordered from NCADI's Web site or by calling (800) 729-6686 (United States only).

Electronic copies: Available from the National Clearinghouse for Alcohol and Drug Information (NCADI) Web site.

Print copies: Available from the National Clearinghouse for Alcohol and Drug Information (NCADI), P.O. Box 2345, Rockville, MD 20852. Publications may be ordered from NCADI's Web site or by calling (800) 729-6686 (United States only).

The following are also available:

• Detoxification and Substance Abuse Treatment Quick Guide for Clinicians. See the related QualityTool summary on the Health Care Innovations Exchange Web site.
• Detoxification and Substance Abuse Treatment Quick Guide for Administrators. See the related QualityTool summary on the Health Care Innovations Exchange Web site.
• Detoxification and Substance Abuse Treatment Quick Guide for Physicians.
• KAP KEYS for Clinicians based on TIP 45, Detoxification and Substance Abuse Treatment.

Electronic copies: Available from the National Clearinghouse for Alcohol and Drug Information (NCADI) Web site.

Print copies: Available from the National Clearinghouse for Alcohol and Drug Information (NCADI), P.O. Box 2345, Rockville, MD 20852. Publications may be ordered from NCADI's Web site or by calling (800) 729-6686 (United States only).

Electronic copies: Available from the National Clearinghouse for Alcohol and Drug Information (NCADI) Web site..

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

Guidelines represented on the NGC Web site are submitted by guideline developers, and are screened solely to determine that they meet the NGC Inclusion Criteria which may be found at http://www.guideline.gov/about/inclusion.aspx .

NGC, AHRQ, and its contractor ECRI Institute make no warranties concerning the content or clinical efficacy or effectiveness of the clinical practice guidelines and related materials represented on this site. Moreover, the views and opinions of developers or authors of guidelines represented on this site do not necessarily state or reflect those of NGC, AHRQ, or its contractor ECRI Institute, and inclusion or hosting of guidelines in NGC may not be used for advertising or commercial endorsement purposes.

Readers with questions regarding guideline content are directed to contact the guideline developer.