Psychiatric Comorbidity

Educational Objectives

The goal of this program is to improve management of patients who have comorbid psychiatric and substance use disorders. After hearing and assimilating this program, the clinician will be better able to:

1.   Explain why the concept of comorbid psychiatric disorders, as presented in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), is oversimplified.

2.   Discuss whether moderate drinking influences the treatment of major depression.

3.   Describe alcohol dependence types A and B.

4.   Recognize the difficulties of diagnosing primary depression in the presence of current alcohol dependence.

5.   Assess the efficacy of various regimens for treating alcohol-dependent patients with comorbid depression.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Pettinati has received research support from Pfizer and Alkermes. Dr. Oslin and the planning committee reported nothing to disclose.

Acknowledgments

Dr. Oslin was recorded at Managing Depression, Substance Use, and Other Psychiatric Disorders in Later Life, held Sep­tember 25-26, 2008, in Ann Arbor, MI, and sponsored by the Veterans Affairs Ann Arbor Healthcare System. Dr. Pettinati was recorded at Day of Discovery: Co-Occurring Disorders, held September 17, 2009, in Charleston, SC, and sponsored by the Medical University of South Carolina. The Audio-Digest Foundation thanks the speakers and the sponsors for their co­operation in the production of this program.

Substance Abuse and Psychiatric Comorbidity

David W. Oslin, MD, Associate Professor, Division of Addiction and Geriatric Psychiatry, Department of Psy­chiatry, University of Pennsylvania School of Medicine, Philadelphia, and Philadelphia Veterans Affairs Medi­cal Center

Introduction: comorbidity  —  typically thought of as 2 illnesses that interact with each other, and occur more fre­quently together than apart; influence treatment-seeking behavior or treatment outcomes, have negative synergistic effect on morbidity and mortality, and impact treatment decisions; some psychiatric disorders have overlapping symptoms that make it difficult to understand disease interaction; speaker emphasizes that psychiatric comorbidi­ties present complicated picture and may not be amenable to simplistic approach

Moderate drinking: norm for seniors (per studies); believed by patients to confer health benefits, such as helping to prevent heart disease; all antidepressants dispensed with warning to avoid alcohol while taking medication, but many people interpret this as prohibition against drinking at same time as taking pill (eg, they believe it might be acceptable to take antidepressant in morning and drink alcohol in evening)

Self-help measures to improve depression: refrain from drinking alcohol and smoking; exercise; do cognitive be­havioral therapy (CBT) homework

Influence of moderate drinking on treatment of major depression: study of patients ³65 yr of age admitted to ge­riatric psychiatric unit in hospital for major depression; assessed at time of discharge and 3 mo later; no alcohol-de­pendent patients; greatest improvement in depression seen in drinkers, because they had no access to alcohol while in hospital; at 3 mo follow-up, they had not yet returned to habit of moderate drinking; study suggests importance of taking away alcohol while treating depression (circumstantial, but good evidence)

Two large national studies: both algorithmically driven; patients started on selective serotonin reuptake inhibitor (SSRI) and assessed after 3 to 6 wk; if not improved, dosage increased or augmented, or psychotherapy offered; all subjects elderly patients being treated for major depression; few subjects changed their drinking patterns (no drink­ing intervention); remission rates for depression lower in nondependent moderate drinkers, but reason unknown

SSRIs in elderly: most common treatment for elderly with depression, despite paucity of data in literature to demon­strate efficacy for this age group; theorized by some to be helpful in alcohol-dependent adults, but treatment studies “have been a mixed bag”

Alcohol-dependence types A and B: type A patients do not have much psychopathology; most started drinking in later life; psychosocial setting stable; type B patients have much psychopathology; psychosocial setting tends to be unstable; in 2 studies, type B patients had poorer response to SSRI than type A patients (unexpected outcome; fur­ther demonstrates complexity of this issue)

Cognitive deficits: alcohol in quantity can cause acute cognitive deficits; in older adults, those effects both height­ened and prolonged (eg, older adult can show acute effects for £36 hr); unknown whether effects cumulative; in vi­tro data demonstrate neurotoxicity of alcohol, but no specific neuropathology associated with alcohol in vivo (ie, effects all parts of brain equally); in study of nursing home residents with dementia, those with Alzheimer’s disease showed steady decline in Mini-Mental State Score of 2 to 3 points per year, whereas among those with dementia thought to be due to alcohol, scores stabilized at some point without further progression (suggests dementia toxin-related; adds credence to existence of alcohol-associated dementia)

Alcohol and illicit drugs: studies find street drugs not uncommon among patients ³60 yr of age; as with alcohol, some start using later in life

Screening: speaker’s institution screens patients for depression and alcohol and drug use (positive screen for depres­sion followed by standard structured secondary battery of tests); past drug use also considered significant due to long-lasting effects on brain; in primary care setting, one-fifth of patients ³50 yr of age with depression admitted to regular use of illicit drug (approximately half used cocaine and half marijuana)

Why patients use substances: positive or negative influence on affect (eg, reduces pain or suffering, improves sleep); enjoyment; cravings; reflexive use of substance (ie, drinking without any thought of consequences or ben­efit); substance dependence  —  does not represent single disorder; core element for some individuals is emotional aspect, although not all those with substance issues have, eg, bipolar disorder or major depression; classifying de­pendence as comorbidity has negative consequence of limiting substance-abuse treatment in favor of treating de­pression; self-medication  —  patient turns to substance use to deal with emotional and affective dysregulation

Craving: inability to get thoughts of substance “out of head”; drives people to seek substance; some lose capacity to recognize detrimental aspects of alcohol or drug use, which suggests frontal lobe impairment (subtle changes in executive functioning); in speaker’s study, inpatients (³50 yr of age; high socioeconomic level) admitted for alco­hol dependence asked to keep daily diary of affect and cravings; diaries showed that »60% of patients did not have craving; 20% to 25% had high craving even after 21 to 28 days of abstinence; after discharge, most non­cravers continued treatment (predominantly 12-step programs); high cravers had poor outcomes

12-step programs: very effective for people who have mild executive dysfunction (ie, those who drink reflexively if alcohol present; if not present, they do not crave it)

Treatment of comorbidity: overlap in symptoms of drug and alcohol use and other psychiatric disorders makes it difficult to plan treatment; difficulty compounded by fact that both conditions chronic and complex; important to use algorithm for long-range treatment planning (eg, determine how to engage patient in dialogue, how to get him or her to return to clinician); particularly with complex patients, also important to do structured assessments of out­comes (eg, Health Questionnaire Depression Scale [PHQ] or other measurement tool)

Depression and Alcohol Use

Helen M. Pettinati, PhD, Professor, Department of Psychiatry, and Director, Division of Addiction Treatment and Medication Development, University of Pennsylvania School of Medicine, Philadelphia

Prevalence and prognosis: 10% to 20% of patients with alcohol disorder have current depressive disorder and »50% have lifetime depressive disorder (common, but not majority; difficult to distinguish between those with depres­sive disorder and major depression); individuals with both disorders more likely to seek treatment than those with only one; prognosis poor (particularly for alcohol-abuse component); alcohol dependence in general pop­ulation »7.9%, drug dependence 3.5%; both much higher in patients with Axis I comorbidity

References: Greenfield  —  major depression in past year predicted worse drinking outcomes 1 yr after treatment; Hasin  —  diagnosis of major depression associated with higher relapse rate to excessive drinking in alcohol-de­pendent patients

Major assessment issue: diagnosing primary depression in presence of current alcohol dependence; do 2 clearly de­rived diagnoses from Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), insure homo­geneity? (no; patients with depression and alcohol dependence show much heterogeneity; subgroups identified based on which disorder predominates; >1 treatment therefore necessary); does origin of depression determine treatment? (unclear; in outpatient setting, difficult to determine whether depression primary or secondary [much easier when alcoholism treated on inpatient basis, as in past]; study suggests it may not matter; depression should be treated whether primary or secondary to alcoholism); do antidepressants work as intended in presence of exces­sive drinking? (patient may derive some benefit from antidepressants, but unknown how much or whether more benefit would be derived if drinking stopped; effect of alcohol on liver could influence medication efficacy); do anti-alcohol medications work as intended in presence of major depression? (unknown; noncompliance known to be higher if patient has both conditions)

Major treatment issue: treating primary depression in presence of current alcohol dependence and treating alco­hol dependence in presence of major depression; usual practice  —  prescribe antidepressant and suggest support groups or addiction counseling for alcohol dependence; alternative  —  some clinicians treat alcohol dependence to get drinking under control, and then determine whether depression remits; if drinking remits but not depres­sion, prescribe antidepressant; “easier said than done”; clinical data  —  only »12 published studies looking at outcomes for both drinking and depression with use of antidepressants; results mixed

Food and Drug Administration (FDA)–approved medications for treating alcohol dependence: extended-re­lease naltrexone (Vivitrol)  —  injectable; stays in system for 1 mo; can be helpful if compliance in question; acam­prosate, naltrexone, and disulfiram  —  noncompliance high

Major treatment question: should alcohol-dependent patient with depression be treated with combination of 2 FDA-approved medications (one for each disorder) and see if both remit?

Design of speaker’s trial: combined sertraline (£200 mg/day) and naltrexone (100 mg/day), sertraline and pla­cebo, naltrexone and placebo, and double placebo; all patients received CBT with mood component once per week; both medications titrated to above doses or to highest dose tolerated by patient; patients treated for 14 wk; 170 patients (all of whom met DSM-IV criteria for depression and alcohol dependence)

Demographics of study group: no differences across groups; average age 43 yr; more men than women; majority white; not many married at time of study; middle to high socioeconomic status; 14 yr of education, on average; majority had family history of alcohol dependence or of alcohol dependence and depression; 40% to 50% had family history of depression

Clinical severity before treatment: average of 22 yr of problem drinking; average of 3 previous treatments for alco­hol dependence; drank 71% of days in previous month; heavy drinking on 63% of days in previous month (heavy drinking defined as ³5 drinks per day for men, ³4 drinks per day for women; average among study subjects »13 drinks per day); Hamilton Depression score average, 23 points (range 0-50 points)

Side effects: anxiety, irritability, and fatigue most common; headache and nausea lowest in double-placebo group; no significant difference in rate or severity of side effects with double medication

In-treatment outcomes: total abstinence  —  higher rate in double medication group than in other groups; time to re­lapse to heavy drinking  —  98 days in double medication group, significantly less in other groups; no depression (single-digit score)  —  83% of double medication group (many of these same participants who achieved total ab­stinence); surprisingly, naltrexone plus placebo group had higher proportion of nondepressed subjects at end of trial than sertraline plus placebo group (reason unknown); antidepressant alone does reduce depression scores, but at slower rate

Conclusions: significantly more depressed and alcohol-dependent patients with in-trial abstinence who received combination of sertraline and naltrexone, compared to those who received either drug with placebo or double pla­cebo; likewise, double medication group had more nondepressed subjects at end of trial than other groups

Suggested reading

Carpentier PJ et al: Psychiatric comorbidity reduces quality of life in chronic methadone maintained patients. Am J Addict 18:470, 2009; Cerdá M et al: Genetic and environmental influences on psychiatric comorbidity: A systematic review. J Af­fect Disord [Epub ahead of print]; Ford JD et al: Association of psychiatric and substance use disorder comorbidity with cocaine dependence severity and treatment utilization in cocaine-dependent individuals. Drug Alcohol Depend 99:193, 2009; Greenfield SF et al: The effect of depression on return to drinking: a prospective study. Arch Gen Psych 55:259, 1998; Hasin D et al: Effects of major depression on remission and relapse of substance dependence. Arch Gen Psychiatry 59:375, 2002; Hatzenbuehler ML et al: Racial/ethnic disparities in service utilization for individuals with co-occurring mental health and substance use disorders in the general population: results from the National Epidemiologic Survey on Al­cohol and Related Conditions. J Clin Psychiatry 69:1112, 2008; Horsfall J et al: Psychosocial treatments for people with co-occurring severe mental illnesses and substance use disorders (dual diagnosis): a review of empirical evidence. Harv Rev Psychiatry 17:24, 2009; Ilgen MA et al: Continuing care after inpatient psychiatric treatment for patients with psychiatric and substance use disorders. Psychiatr Serv 59:982, 2008; Kampman KM et al: A double-blind, placebo-controlled pilot trial of quetiapine for the treatment of Type A and Type B alcoholism. J Clin Psychopharmacol 27:344, 2007; Kranzler HR et al: Sertraline treatment of co-occurring alcohol dependence and major depression. J Clin Psychopharmacol 26:13, 2006; O’Brien CP et al: Priority actions to improve the care of persons with co-occurring substance abuse and other mental disorders: a call to action. Biol Psychiatry 56:703, 2004; Oslin DW et al: Daily ratings measures of alcohol craving during an inpatient stay define subtypes of alcohol addiction that predict subsequent risk for resumption of drinking. Drug Alcohol Depend 103:131, 2009; Pettinati HM: Antidepressant treatment of co-occurring depression and alcohol dependence. Biol Psychiatry 56:785, 2004; Rus-Makovec M, Cebasek-Travnik Z: Co-occurring mental and somatic diagnoses of alcohol dependent patients in relation to long-term aftercare alcohol abstinence and well-being. Psychiatr Danub 20:194, 2008; Sher L et al: Depressed patients with co-occurring alcohol use disorders: a unique patient population. J Clin Psychiatry 69:907, 2008.