The use of pharmacological and non-pharmacological treatments for addictive disorders and attendant psychiatric comorbidity requires an independent status for each disorder. Although there are relative contraindications for the use of pharmacological agents in addictive disorders alone, these agents can be used as indicated for comorbid psychiatric disorders in patients addicted to drugs and alcohol.
TREATMENT FOR THE COMORBID DISORDERS
It is widely acknowledged that the treatment of addictive disorders can be difficult without adequate treatment of the psychiatric disorder. For instance, a schizophrenic patient who is hallucinating and delusional, but who also uses alcohol or drugs, cannot participate in treatment for the addiction without adequate control over the psychosis. Likewise, a manic patient who is euphoric and delusional, an anergic depressive patient, or an agoraphobic patient addicted to alcohol and/or other drugs will have difficulty cooperating with addiction treatment.1,2
When feasible, nonpharmacological treatment of a comorbid addictive disorder is preferable for a schizophrenic, manic, depressive, or phobic patient to enhance compliance with psychiatric treatments. It is known that poor control of the addictive disorder can lead to an unfavorable prognosis for the concurrent psychiatric disorder. The prognosis of combined psychiatric and addictive disorders follows more closely that of the addictive disorders. Thus, treatment of the addictive disorder seems necessary to improve the course of either disorder.3,4
Pharmacological agents have limitations in the addicted population. Medications may impair cognition and blunt feelings, sometimes subtly. Clinicians treating addictive disorders advocate that the alcoholic or addict needs a clear sensorium and access to emotions to make fundamental changes in them. The recovering alcoholic or drug addict must take an active part in changing attitudes and in abandoning the long-held belief that alcohol and/or drugs can "treat" life problems and uncomfortable psychological states.5
Symptoms such as anxiety and depression in recovering addicts might be vital to recovery, and pharmacotherapy to treat such symptoms must be considered carefully in this context.5 Clinically, anxiety and depression can provide the motivation to change when otherwise the sufferer has little awareness of the need to alter behavior. A commonly used expression to explain this practice among recovering individuals is "no pain, no gain"
Standard of Care
After detoxification and stabilization with pharmacologic agents, the current treatment of choice for addictive disorders is nonpharmacological. Further, several studies have shown that treating addictive disorders with abstinence alone results in improvement of the psychiatric syndromes associated with the alcohol and/or drug use or addiction. Severe syndromes induced by alcohol that may meet criteria for major depressive and anxiety disorders in DSM-IV resolve within days to weeks with abstinence. Likewise, manic syndromes induced by cocaine resolve within hours to days, and schizophrenic-like syndromes (e.g., hallucinations and delusions) induced by cocaine and PCP often resolve within days to weeks with abstinence.5,6
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.7-9
PSYCHOTROPICS FOR ADDICTIVE DISORDERS
Only limited studies are available investigating the use of antidepressants in the treatment of addictive disorders or for the psychiatric complications of alcoholism and drug addiction. In general, antidepressants do not appear to alter the course of alcoholism or the symptoms of depression from the alcoholism.10-12 These studies, however, were limited by
* a short evaluation period;
* use of other medications in addition to the antidepressant;
* inadequate definitions of depression and alcoholism;
* poor differentiation between depression from other causes and alcoholism; and
* failure to measure antidepressant blood levels.10-12
Objective markers, such as the dexamethasone suppression test (DST), do not distinguish between alcoholism and depression from other causes. Some studies used a 2-week cutoff to attribute a positive DST to causes other than alcoholism, but other clinical studies found significant signs and symptoms of depression at 6 weeks that could be attributed to the alcoholism. 13,14
In one controlled study, depressed nonalcoholics who had therapeutic blood levels of imipramine showed improvement in their depression as measured by a self-report rating scale, whereas depressed alcoholics who had subtherapeutic blood levels showed no improvement in their depression.12 Another controlled study found that depressed alcoholics who received desipramine did not show improvement in abstinence rates, but did show less depression that correlated with abstinence.15
Results from controlled studies have not confirmed a role for antidepressants in cocaine addiction.
Lithium has been used in both uncontrolled and controlled trials for depressed and nondepressed alcoholics. While early open-label and uncontrolled studies suggested improved abstinence in alcoholics, especially those with a history of affective disorder, the criteria for alcoholism and depression differed widely, methods for measuring treatment response varied, and dropout rates were 30% to 59%. 16,20
In a multisite, double-blind, placebo-controlled study, the effect of lithium versus placebo in 200 randomly assigned alcoholics with no other psychiatric illness was compared to 200 alcoholics with a diagnosis of major depressive disorder or dysthymic disorder. While significant differences were found among the four groups (i.e., depressed alcoholics on lithium or placebo and nondepressed alcoholics on lithium or placebo), the depressed alcoholics on lithium tended to show the poorest abstinence rate.20
In another study, alcoholics compliant with lithium therapy were followed for 18 months. Lithium blood levels were equal to or greater than 0.7 mEq/L, while compliance was measured by self-report in the placebo group. Those who were maintained on active drugs continued abstinence at a higher rate than placebo-compliant patients. Lithium therapy, however, did not reduce the frequency of drinking after relapse, nor did the depressed alcoholics respond differently than nondepressed alcoholics to the antidepressant effect of lithium.16
Antipsychotics have not been investigated extensively.21 Theoretical consideration suggests that dopamine (DA) blockade should intensify the drive to drink or to use other drugs by reducing the stimulation of DA by blockade of postsynaptic neurons in the reinforcement area. The putative "addiction substrate" is specifically the mesolimbic pathway that contains DA neurons extending from the ventral tegmentum to the nucleus accumbens. Clinically, there is no indication that neuroleptics alter the course of alcoholism or drug addiction alone.21
Benzodiazepines and their agonists have not been extensively studied as a substitute for alcohol, ostensibly because of the clinical and research experience that shows alcoholics tend to relapse to alcohol while on benzodiazepines. Further, benzodiazepines as a class are addicting and produce significant pharmacological tolerance and dependence.22'23 Recent controlled studies found that symptoms of anxiety, depression, and insomnia worsened despite continued use of benzodiazepines.22-24 Thus, these findings did not support the value of long-term benzodiazepine therapy.
PSYCHOTROPICS FOR COMORBID PSYCHIATRIC DISORDERS
Because alcohol and drugs can induce almost any psychiatric symptom or sign or mimic any psychiatric disorder, their effects must always be considered before a comorbid or dual diagnosis is established or treated.25
With an understanding of the interactions between psychiatric syndromes and alcoholism or drug addiction, a rational approach can be applied to the use of pharmacological therapies in comorbid disorders. The use of medications for psychiatric symptoms should only begin after the knowledge of the natural history of the addictive disorder and other psychiatric disorders is clarified.26 Further, skill must be developed to identify the respective roles of addictive and other psychiatric disorders in the generation of psychiatric symptoms.27
Generally, psychiatric symptoms induced by alcohol or drugs resolve within days to weeks.25,28-31 Moreover, studies show that nonanxious and nondepressed alcoholics continue to drink despite alcohol-induced anxiety and depression and not because of these symptoms.25»28 Alcohol use was negatively correlated with depressive episodes in nonalcoholics with bipolar or unipolar disorders.25'28 While alcohol consumption was elevated in the manic phase, so were other hyperactive behaviors.29 In many studies, the prevalence rates for anxiety and affective disorders in alcoholics were not greater than that for nonalcoholics.25,28-30
A retrospective history of psychiatric symptoms can often lead to an inflated diagnosis of these disorders because of rationalizations and minimizations regarding drinking and drug use by the individual.31 Typically, psychiatric symptoms are emphasized by both the patient and the psychiatric examiner. Longitudinal observation frequently clarifies the role of alcohol and drugs in the production of anxiety, affective, psychotic, or personality symptoms, particularly if objective criteria are relied on in addition to the addict's subjective report.6»29 Also, specific treatment of addictive disorders can result in improvement of mood, psychotic, and personality disturbances if related to the alcohol or drug use. Mood lability and personality states can be a manifestation of addictive disorders, and treatment of the addictive disorder can lead to stabilization of these psychiatric symptoms.30
Prevalence rates for the comorbidity of anxiety and addiction disorders range from 5% to 20% in epidemiological and clinical studies.25,28-30
Anxiety is necessary for normal living but is abnormal when it becomes excessive and interferes with routine daily function. Normally, anxiety signals the individual to action or arousal for self-protection. When anxiety is overwhelming, it can cause the nervous system to "overact," paralyzing the individual and inhibiting the normal responses from internal and external cues. The individual can become chronically maladaptive to the internal or the external environment, thus reducing normal responses to stimuli. Pharmacological agents can ameliorate the incapacitating arousal characteristic of anxiety disorders.
These antianxiety agents can also 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 must 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.
Depressants (e.g., alcohol) can produce anxiety during withdrawal, and stimulants (e.g., cocaine) can produce anxiety during intoxication.25 Because alcoholics and drug addicts are in a relatively constant state of withdrawal (it is impossible to maintain a constant blood level), they regularly experience anxiety from pharmacological withdrawal (dependence). As the alcohol and drug use become more chronic, the anxiety from pharmacological dependence can become increasingly severe.25'28 Relapse and/or periods of abstinence (sometimes prolonged - weeks or months) must be considered (confirmation of 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 is often sufficient in clinical practice.29,30,32-34
Treatment is indicated when the anxiety persists after adequate effort in a recovery program for addiction. A thorough evaluation to assess whether the individual is abstinent, using continuing treatment and/or attending self-help meetings, and using other forms of addiction therapy is usually necessary before a diagnosis of psychiatric comorbidity can be definitively established. After such an evaluation, treatment of the anxiety disorder can proceed separately from similar symptoms arising from the addictive disorder.35
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 should then be attempted to see if the medication is still necessary.35
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 addiction must be treated independently of the anxiety disorder and vice versa.36
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 (apprehension), unpleasant tenseness, and many more.34
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.35 As noted earlier, the benzodiazepines can cause significant problems in addicted and nonaddicted patients. Thus, they are not generally recommended for alcoholics and drug addicts or for long-term treatment of anxiety or depressive disorders. Benzodiazepines can produce addiction, tolerance, and dependence on their own, especially in those patients already exhibiting addiction to a drug or alcohol.22'23 Anti-depressants such as imipramine and nortriptyline and SSRIs such as fluoxetine have a low addiction potential and can be used with relative safety in either the addicted or the nonaddicted patient.37 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.35
Prevalence rates for the comorbidity of depressive and addictive disorders range from 5% to 25% in epidemiological and clinical studies#25,28-30
Depressive disorders include major depressive and dysthymic disorders, which can occur independently with addictive disorders, or similar depressive symptoms can be induced by alcohol and drug disorders.
Depression can be viewed as protective and associated with "healing" in many conditions involving emotions. For example, a grief reaction is an expected experience after a loss, with depression an essential emotion in this process. Recovery from an addictive disorder has been compared to a grief reaction because of losses suffered by the addict (e.g., alcohol, drugs, relationships). Likewise, and analogous to the role of anxiety, depression is also a part of the healing process the addict experiences during recovery from addictive disorders.
Depressant drugs (e.g., alcohol) can produce depression during intoxication, and stimulant drugs (e.g., cocaine) can produce depression during withdrawal.25 These effects may be prolonged with certain drugs that linger in the body (i.e., stored in fat), such as cannabis and benzodiazepines. These drugs can produce depression or anxiety that is indistinguishable from other psychiatric causes of depression.25»28 Therefore, they must be considered causative whenever depression is present, and the possibility of addiction must 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. Major depressive disorder is more common in older individuals and in females and can be difficult to distinguish from the depression induced by alcohol or drugs.29,30,33,34
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 must be weighed, as is the case with anxiety disorders.
Antidepressants are the mainstay of 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 disorders.34
Depressive disorders are thought to have a significant biological component, including deficiencies in such CNS neurotransmitters as serotonin, norepinephrine, and dopamine. Interestingly, these neurotransmitters are also affected by alcohol and other drugs of addiction.26 These agents are thought to act by enhancing the activity of these neurotransmitters, ultimately alleviating depression and stabilizing mood. Examples of several different antidepressants distinguished by their actions on neurotransmitters are given in Table 1.
Prevalence rates for the comorbidity of bipolar and addictive disorders range from 30% to 60% in epidemiological and clinical studies.25,28-30
Mania is a condition associated with elevated mood, grandiosity, hyperactive behavior, poor judgment, and lack of insight. The manic patient will show excesses such as spending sprees, sexual promiscuity, intrusiveness, and abnormal alcohol and drug use. A manic episode can follow, precede, or alternate with depressive episodes.34
The manic state can be produced by stimulants (e.g., cocaine) during intoxication, and during withdrawal from depressants (e.g., alcoJ10I) 29,30,33,34 A period of confirmed abstinence is usually 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.25'28-30
Mood stabilizers control bipolar disorder in patients with or without comorbid addictive disorder. These medications can control either the manic or depressed phase, or both.
Manic episodes can occur cyclically, alternatively, and concurrently with depressed episodes. One theory of the pathogenesis of bipolar disorder is thought to involve the neurotransmitter norepinephrine (i.e., excessive in mania and deficient in depression).35
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 mg to 2400 mg to achieve plasma levels in the 0.5 to 1.5 mEq/L range.35
Biochemical Activity of Commonly Used Antidepressant Drugs
Anticonvulsant mood stabilizers include divalproex sodium and carbamazepine. They can be effective in controlling mania and, some evidence suggests, in comorbid addictive disorders as well. One theoretical explanation for their mechanism of action 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.35
Prevalence rates for comorbidity of schizophrenic and addictive disorders range from 40% to 80% in epidemiological and clinical studies25,28-30
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 while behavioral, group, and individual psychotherapy are more effective for the negative symptoms. Newer agents such as clozapine and risperidone may be more effective in treating both the positive and negative symptoms.35
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 drugs of addiction, but as with anxiety, depression, or mania, medications can be started at almost any time if the psychosis is persistent and waiting is not possible.25»28 Moreover, the greater the number of psychiatric admissions, the greater the probability of a chronic mental disorder associated with the comorbid addictive disorder.
High or moderate potency neuroleptics are generally the agents of choice in the treatment of schizophrenia (e.g., haloperidol or thiothixene).35 The potency is determined by the drug's ability to block the action of the neurotransmitter dopamine at postsynaptic DA2 receptor sites (Table 2).
Newer antipsychotics include clozapine and risperidone, both of which cause fewer extrapyramidal effects. This may be of critical importance, because clinical experience (and a few studies) suggest that patients with comorbid disorders may show greater compliance with psychiatric and addiction treatments when receiving agents that produce fewer extrapyramidal symptoms.35
Hallucinations and delusions that occur in other states, such as dementia, delirium, and drug-induced states secondary to such agents as PCP (phencyclidine), can all benefit from antipsychotic treatments. While these drugs must be taken regularly to suppress or prevent the recurrence of a chronic psychosis, they can be discontinued in acute episodes, such as brief reactive psychosis. A drug holiday from medications can be attempted after a few months (or sooner) if addictive drugs are clearly implicated as the principal cause of the hallucinations and delusions35 (Table 2).
Medications are essential in the treatment of major mental disorders, especially in the presence of a comorbid addictive disorder. The agonizing hallucinations (e.g., voices telling patients they are bad and deserve to die) and delusions (e.g., making patients think they are going to be seriously harmed or someone they love will be harmed) can often be minimized by pharmacotherapy. By taking mood stabilizers, the out-ofcontrol manic patient is spared embarrassing and devastating episodes that can jeopardize careers, relationships, and even their lives. The anxious and depressed patient can benefit from agents prescribed to quiet symptoms that can be incapacitating to the sufferer. In addition, these medications can enhance recovery from addictive disorders by allowing the individual to be relatively free from the psychiatric symptoms not directly related to the addiction.
Potencies and Side Effect Profiles of Various Psychotropic Drugs
Medications have minor and major adverse effects, and, indeed, some are addictive. As examples, benzodiazepines can be especially problematic to the recovering alcoholic or addict, while antipsychotic and antidepressant medications with anticholinergic effects are sometimes used addictively. Also, these medications can produce anxiety and depression during chronic use (from pharmacological dependence).
Antipsychotics can produce sedation, hypotension (at times causing lightheadedness and syncope 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.35 This symptom usually requires a beta blocker if a decrease in the antipsychotic dose does not work.35 Alternatively, switching to risperidone may accomplish the intended effect while avoiding intolerable neurological syndromes.
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 has also been reported with most antidepressant medications.35
The SSRIs are preferred in patients with comorbid addiction because of their lack of addiction potential, anticholinergic effects on the sensorium, and risk of lethal effects from overdose.
The recovering alcoholic or addict must have a clear mind and a stable mood.36 Medications have a tendency, sometimes subtly and other times obviously, to dull the sensorium and thinking and/or blunt or disrupt the emotional state. Addicts must eventually change and control feelings to remain sober and also to comply with psychiatric management. The addict's ability to use the 12 steps of Alcoholics Anonymous (AA) and accept psychiatric advice will depend on clear thinking and emotional balance, which is stressed as central to the recovery process in AA.
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.36
The key to an optimal therapeutic approach is to understand and be skilled in both addictive and psychiatric disorders. It is best that the staff and therapeutic setting for the patients with psychiatric and addictive comorbidity be integrated for diagnosis and treatment. It is no longer useful to argue over ideology while patients continue to be inadequately treated, with the potential for serious consequences. Integration will serve as a clear indication to the patient that one disorder is not more or less important than the other. The cornerstone of integration is acceptance by staff and patients that while addictive and psychiatric disorders are independent, they also interact.38
1. Alterman AI, Erdlen FR, Murphy E. Alcohol abuse in the psychiatric hospital population. Addici Behav. 1981; 6:69-73.
2. Kofoed L, Kanie J, Walsh T. Outpatient treatment of patients with substance abuse and coexisting psychiatric disorders. Am J Psychiatry. 1986; 143:867-872.
3. Drake RE, Osher FC, Wallach MA. Alcohol use and abuse in schizophrenia: a prospective community study. J Neru Ment Dis. 1989; 177:408-414.
4. Bernadt MW, Murray RM. Psychiatric disorder, drinking and alcoholism: what are the links? Br J Psychiatry. 1986; 148:393-400.
5. Miller NS. Comorbidity of psychiatric and alcohol/drug disorders: critical overview and future directions for "dual diagnosis." J Addict Disord. 1993; 12:5-16.
6. Schuckit MA, Montero MG. Alcoholism, anxiety, depression. Br J Addict. 1988; 83:1373-1380.
7. Hoffman NG, Miller NS. Treatment outcome for abstinence-based programs. Psychiatric Annals. 1992; 22:402407.
8. Keso L, Salaspuro M. Inpatient treatment of employed alcoholics: a randomized clinical trial on Hazelden-type and traditional treatment. Alcohol Clin Exp Res. 1990; 14:584-589.
9. Walsh EC, Hingson RW, Merrigan DM, et al. A randomized trial of treatment options for alcohol abusing workers. N Engl J Med. 1991; 325:775-782.
10. Liskow BI, Goodwin DW. Pharmacologic treatment of alcohol intoxication, withdrawal and dependence: a critical review. J Stud Alcohol. 1987; 8:356-370.
11. Ciraulo DA, Jaffe JH. Tricyclic antidepressants in the treatment of depression associated with alcoholism. J Clin Psychopharmacol. 1981; 1:146-150.
12. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA. Imipramine disposition in alcoholics. J Clin Psychopharmacol. 1982; 2:2-7.
13. Dackis RA, Stuckey RF, Gold MS, Pottash AL. Dexamethasone suppression testing of depressed alcoholics. Alcohol Clin Exp Res. 1986; 10:59-60.
14. Khan A, Ciraulo DA, Nelson WH, Becker JT, Nies A, Jaffe JH. Dexamethasone suppression in detoxified alcoholics: clinical implications. J Clin Psychopharmacol. 1984; 4:94-97.
15. Mason BJ, Kocsis JH. Desipramine treatment of alcoholism. Psychopharmacol Bull. 1991; 27:155-161.
16. Fawcett J, Clark DC, Gibbons RD, et al. Evaluation of lithium therapy for alcoholism. J Clin Psychiatry. 1984; 45:494-499.
17. Kline NS, Wren JC, Cooper TB, Varga E, Canal O. Evaluation of lithium therapy in chronic and periodic alcoholism. Am J Med Sci. 1974; 268:15-22.
18. Merry J, Reynolds CM, Bailey J, Coppen A. Prophylactic treatment of alcoholism by lithium carbonate. Lancet. 1976; 2:481-482.
19. Young LD, Patel M, Keller MH. The effect of lithium carbonate on alcoholism in 20 male patients with concurrent major affective disorder. Currents in Alcoholism. 1981; 8:175-181.
20. Dorus W, Ostrow DG, Anton R, et al. Lithium treatment of depressed and nondepressed alcoholics. JAMA. 1989; 262:1646-1652.
21. Miller SI, Frances RJ, Holmes DJ. Psychotic medications. In: Miller WR. Alcoholism Treatment Approaches. Elmsford, NY: Pergamon Press; 1990:231-241.
22. Rickels K, Schweizer E, Case G, Greenblatt DJ. Longterm therapeutic use of benzodiazepines, I: effects of abrupt discontinuation. Arch Gen Psychiatry. 1990; 47:899-907.
23. Schweizer E, Rickels K, Case G, Greenblatt DJ. Longterm therapeutic use of benzodiazepines, II: effects of gradual taper. Arch Gen Psychiatry. 1990; 47:908-915.
24. Miller NS, Gold MS. Abuse, addiction, tolerance and dependence to benzodiazepines: in medical and nonmedical populations. Am J Alcohol Drug Abuse. 1991; 17:27-39.
25. Miller NS, Mahler JC, Belkin BM, Gold MS. Psychiatric diagnosis in alcohol and drug dependence. Ann Clin Psychiatry. 1991; 3:79-89.
26. Miller NS. The psychiatric consequences of alcohol and drugs of abuse and addiction. In: The Pharmacology of Alcohol, Drugs of Abuse and Addiction. New York, NY: Springer-Verlag; 1991:77-88.
27. Fine J, Miller NS. Methodological approach to psychiatric and addictive disorders in drug and alcohol dependence. In: Comorbidity of Addictive and Psychiatric Disorders. New York, NY: Haworth Press; 1993.
28. Blankfield A. Psychiatric symptoms in alcohol dependence: diagnostic and treatment implications. J Subst Abuse Tr-eat. 1986; 3:275-278.
29. Schuckit MA. Alcoholism and other psychiatric disorders. Hosp Community Psychiatry. 1982; 43:53-57.
30. Penick EC, Powell BJ, Nickel EJ, et al. Comorbidity of lifetime of psychiatric disorder among male alcoholics. Alcohol Clin Exp Res. 1994; 18:1289-1293.
31. Tamerin JS, Mendelson JH. The psychodynamics of chronic inebriation: observations of alcoholics during the process of drinking in an experimental group setting. Am J Psychiatry. 1969;125:886-899.
32. Schuckit MA. Dual Diagnosis: Psychiatric Picture Among Substance Abusers. Principles of Addiction Medicine. Washington, DC: American Society of Addiction Medicine; 1994.
33. Brown SA, Schuckit MA. Changes in depression among abstinent alcoholics. J Stud Alcohol. 1988; 49:412-417.
34. American Psychiatric Association. Diagnostic and Statistical Manual. 4th ed. Washington, DC: American Psychiatrìc Association; 1994.
35. Janicak PG, Davis JM, Preskorn SH, Ayd F Jr. Principles and Practice of Psychopharmacotherapy. Baltimore, MD: Williams & Wilkins; 1993.
36. Miller NS, Gold MS. The psychiatrist's role in integrating pharmacologic and nonpharmacologic treatments for addictive disorders. Psychiatric Annals. 1992; 22:436-440.
37. Schweizer E, Rickels K, Weiss S, Zavodnick S. Maintenance drug treatment for panic disorder, I: results of a prospective, placebo-controlled comparison of alprazolam and Imipramine. Arch Gen Psychiatry. 1993; 50:51-60.
38. Minkoff K. Models for addiction treatment in psychiatric populations. Psychiatric Annals. 1994; 24:412-417.
Biochemical Activity of Commonly Used Antidepressant Drugs
Potencies and Side Effect Profiles of Various Psychotropic Drugs