Bipolar Disorder: Part 2

Highlights from the 10th Annual Psychiatry Review: Recent Advances in the Treatment of Bipolar Disorder,
presented by the University of Minnesota Medical School

Educational Objectives

The goal of this program is to improve the management of bipolar disorder. After hearing and assimilating this pro­gram, the clinician will be better able to:

1.   Differentiate the symptoms of bipolar disorder from those of substance use disorder.

2.   Describe substance use states that can mimic psychiatric disorders.

3.   Integrate treatment of  bipolar disorder with that of a comorbid substance use disorder.

4.   Discuss components shared by borderline personality disorder and bipolar disorder that are particularly ame­nable to dialectical behavior therapy.

5.   Apply the principles of dialectical behavior therapy to the treatment of bipolar disorder.

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 faculty and planning committee reported nothing to disclose. In her lecture, Dr. Specker discusses the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Drs Specker and Miller were recorded at 10th Annual Psychiatry Review: Advances in the Treatment of Bipolar Disorder, held September 14-15, 2009, in Minneapolis, MN, and sponsored by the University of Minnesota Medical School. The Au­dio-Digest Foundation thanks the speakers and the University of Minnesota Medical School for their cooperation in the pro­duction of this program.

Chemical Dependency in Bipolar Disorder

Sheila M. Specker, MD, Associate Professor, Department of Psychiatry, University of Minnesota Medical School, Minneap­olis

Introduction: substance use is rule rather than exception in bipolar disorder; 60% of people with bipolar disorder have co-occurring lifetime substance use disorder (SUD); bipolar disorder type I has highest rate of comorbid sub­stance use disorder among psychiatric disorders; alcohol most common substance of abuse (»46% lifetime preva­lence), followed by marijuana (30%-50%), and amphetamines and cocaine (20%-35%); sedatives and opioids less frequently abused

Comorbid bipolar disorder and SUD: worse prognosis; poorer response to lithium; slower stabilization in hospital; more frequent suicide attempts and hospitalizations; more treatment noncompliance; higher risk for relapse to sub­stance use than with SUD alone; increased risk for eg, financial problems, family problems, homelessness, vio­lence, incarceration

Problems making diagnosis in dual disorders: substance abuse in individual with bipolar disorder possibly self-medication that resolves with treatment of bipolar disorder; criteria for diagnoses overlap; difficult to differentiate substance-induced syndromes from other psychiatric disorders; information often incomplete and/or inaccurate

Substance use states that can mimic psychiatric disorders: depression  —  can be caused by depressants (eg, alco­hol, sedatives); mania  —  can be caused by stimulants; psychosis  —  can be caused by cocaine, amphetamines, hallucinogens, and cannabis; early recovery  —  often causes symptoms opposite of intoxication symptoms (eg, withdrawal from stimulant can cause depression); mood swings may persist for £1 yr during recovery (may re­quire treatment)

Impulsivity: common as feature of substance-use conditions, but also symptom of attention-deficit disorder (ADD) and mania; may be difficult to differentiate between impulsivity caused by SUD, bipolar disorder, ADD, or un­derlying personality

Substance abuse as cause of psychiatric disease: unclear whether this occurs; more likely that illnesses can be ex­pedited, rather than caused by, substance abuse

Reasons to differentiate: those with dual diagnoses may need additional services; may have more severe pathology; may have reduced resources and/or support systems; concomitant alcohol use reduces efficacy of and compliance with treatment; prognosis may be worse

Making the psychiatric diagnosis: establish chronologic history; do psychiatric symptoms persist during periods of abstinence? do they occur during periods of abstinence? did mood symptoms occur before onset of substance use?

Self-medication hypothesis: those with psychiatric disorders use substances to  —  reduce anxiety; blunt or control affect; sleep; treat pain; treat other somatic symptoms; improve attention; relieve withdrawal

Association between specific substances and conditions: bipolar disorder more common in those with cocaine de­pendence than in those with alcohol dependence; depression more often associated with alcohol and opioid use; of mood and anxiety disorders, mania associated with highest probability of drug dependence; lifetime occurrence of bipolar disorder in those who abuse drugs (excluding alcohol), 3% to 11%

Risk factors for developing drug abuse in bipolar patients: male sex; lower educational level; fewer social sup­ports; presence of other Axis I disorders; perhaps earlier onset of mood symptoms; more mania than depression; rapid cycling or mixed state

Treatment compliance in SUDs: associated with better compliance  —  being employed; older age; more education; more social supports; associated with poor compliance  —comorbidity; severity of psychiatric symptoms; cognitive impairment; poor social supports

Pharmacotherapy for Substance Use

Disulfiram (eg, Antabuse): approved by Food and Drug Administration (FDA) for treatment of alcoholism; inhibits liver enzyme and causes accumulation of toxic precursor; results in flushing, nausea, and vomiting if patient con­sumes alcohol; found to decrease frequency of drinking, but not associated with long-term improvement; risk for liver toxicity requires monitoring via liver function tests; decreases activity of enzyme that breaks down dopamine, thereby increasing dopamine levels and creating risk for psychosis; works best with impulsive drinkers or in high-risk situations; use as adjunct to psychosocial treatments; small percentage of individuals can drink alcohol while taking disulfiram without suffering ill effects  (most likely have alternative metabolic pathway); consider having patient take it in presence of witness (clinician or family member) to create accountability; speaker uses for patients in early recovery or during exposure to high-risk situation

Naltrexone: approved by FDA for alcoholism; blocks μ receptor, which theoretically leads to lower craving, lower al­cohol consumption, and decreased reward; available as monthly injection; disadvantage  —  because it blocks opi­oid receptors, patients unable to benefit from opioids in emergent situations; results of studies  —  mixed; early trials showed less craving, fewer drinking days, and delayed time to first drink; large multicenter trial found no difference in alcohol use; speaker suggests using in situations of craving; most trials used 50-mg dose; several studies suggest need for higher dose (£150 mg); speaker considers it moderately effective treatment

Trials in population with alcoholism and bipolar disorder: fewer studies; open-label study of 34 outpatients found improvement in mood symptoms, days of use, and craving; medication well tolerated; investigators theorized that naltrexone might indirectly improve mood symptoms via improved self-esteem and better compliance with medication regimens (related to reduced alcohol consumption), and by removing effect of substance; double-blind placebo-controlled pilot study of 50 outpatients showed trend toward fewer drinking days, lower cravings, and reduced liver enzymes in those on naltrexone, compared to those on placebo

Naltrexone and disulfiram combination: study of each agent individually, each agent with placebo, combination of naltrexone and disulfiram, and double placebo showed improvement in all groups (patients likely receiving ad­junct therapies); those with active medications had more continuous weeks of abstinence and fewer drinking days, but no difference in percentage of days abstinent; no advantage seen with receiving both medications; di­sulfiram associated with greater reduction in g-glutamyl transpeptidase (GGT; enzyme often elevated in abusers of alcohol), lower craving, and lower compulsion than naltrexone

Acamprosate: approved by FDA for use in treating alcoholism; amino acid derivative that affects balance between neurotransmitters glutamine (excitatory) and g-aminobutyric acid (GABA; inhibitory); 7 European trials showed moderate effect size; rates of abstinence increased if acamprosate combined with psychosocial interventions; of inferior efficacy when compared directly to disulfiram; United States trial showed acamprosate most effective in highly motivated individuals

Other agents: valproate  —  small trial showed significantly lower number of heavy drinking days, improvement in affective symptoms, and decrease in GGT; topiramate  — in theory, could help control impulsivity, but no data available; carbamazepine  —  some evidence of efficacy for individuals with bipolar disorder and comorbid co­caine abuse; lithium  —  little or no data available; requires more monitoring (speaker does not use often); drug choice depends on patient characteristics

Psychosocial treatment: important; outcomes better when treatment for bipolar disorder and substance use disorder integrated; self-help groups useful (support from other people in recovery especially important); social stability and adherence to treatment also important

Cognitive behavioral therapy (CBT): study showed medical management plus CBT increased number who com­pleted treatment, compared with group receiving medical management alone; improvement in mood seen, and integrated treatment well-liked by patients

Conclusions: SUDs and bipolar disorders highly associated and have increased risks for poor outcomes; essential to integrate treatment for both; addiction pharmacotherapies and CBT shown to be beneficial, but much additional re­search needed; treatment compliance essential

Dialectical Behavior Therapy for Bipolar Disorder

Michael J. Miller, PsyD, Assistant Professor, Department of Psychiatry, University of Minnesota Medical School, Minne­apolis

Introduction: evidence for efficacy of dialectical behavior therapy (DBT) in treatment of bipolar disorder mostly an­ecdotal at present (only one study completed); commonalities between bipolar disorder and borderline personality disorder  —  suicidal and parasuicidal thinking, emotional dysregulation (affective instability or lability), cognitive dysregulation (paranoid ideation and dissociative symptoms); patients with bipolar disorder find DBT concepts which target emotional and behavioral dysregulation most useful

Biosocial theory: borderline personality disorder  —pervasive dysfunction of emotion regulation system; involves bi­ologic factors combined with invalidating environment (can result from mismatch between personalities of parent and child, as well as from abuse); emotional vulnerability  —  inability to modulate emotions; leads to high sensitiv­ity, high reactivity, and slow return to baseline

Five functions of all comprehensive treatments: 1) enhance capabilities; 2) improve motivational factors; 3) assure generalization to natural environment (so skills learned in practitioner’s office can be extended to patient’s natural environment); 4) enhance therapist’s capabilities and motivation to treat effectively (eg, through support from col­leagues); 5) structure environment (eg, coordinate with other providers such as social workers, psychiatrists, or psy­chologists)

Standard modes of DBT: individual outpatient psychotherapy; outpatient group skills training; telephone consulta­tion; therapists’ consultation meeting; uncontrolled ancillary treatments (pharmacotherapy; acute inpatient care)

Targets for DBT skills training: convert severe behavioral dyscontrol to control; decrease life-threatening behav­iors, therapy-interfering behaviors (on part of therapist or patient), quality-of-life interfering behaviors (all those that do not fall into life-threatening behavior category); increase behavioral skills through mindfulness, interper­sonal skills (concepts based on assertiveness training), emotional regulation, and distress tolerance

“Wise mind” practices: data show that therapist needs to practice mindfulness in interactions with patients; ob­serves, describes, and participates; cognitive behavioral techniques used in DBT problem-solving considered stan­dard in any behavioral therapy

Self-verification theory: validation by others promotes self-verification; patients with bipolar disorder “get invali­dated a lot,” resulting in invalidation of their own self-constructs (ie, feel “crazy”, out of control, unlike anyone else); this thinking leads to cycle of arousal and increased sense of being out of control, and eventually results in failure to process new information and incapability of new learning (limbic system activated, which causes other portions of brain to shut down)

Dialectics: approach considers everyone’s opinion and perspective valid; attempts to resolve conflicts by finding middle ground; balances change with acceptance, and problem solving with validation; components of dialectical communication include irreverence, reciprocation, consultation with patient, team consultation, and environmental intervention (eg, therapist may intervene if he or she believes medication change needed)

DBT for adolescents with bipolar disorder: only study done using DBT for bipolar disorder; 10 patients received DBT for 1 yr; incorporated family skills, individual therapy, and pharmacotherapy; results  —  9 of 10 completed; improvement seen in suicidality, nonsuicidal self-injurious behavior, emotional dysregulation, and depressive symptoms

DBT with adults with bipolar disorder: University of Colorado psychiatrist employs DBT with adult patients with bipolar disorder (results not published); attempting to decrease likelihood of suicide; PLEASE master skills  —  treating physical illness (taking all of one’s medications on consistent basis); balanced eating; avoiding mood-al­tering substances; balanced sleep; balanced exercise); teaches patients how to care for themselves physically, and, by so doing, reduce sensitivity to their emotions

Suggested Reading

Brown ES et al: Naltrexone in patients with bipolar disorder and alcohol dependence. Depress Anxiety  23:492, 2006; Buonopane A, Petrakis IL: Pharmacotherapy of alcohol use disorders. Subst Use Misuse 40:2001, 2005; Comtois KA, Linehan MM: Psychosocial treatments of suicidal behaviors: a practice-friendly review. J Clin Psy­chol 62:161, 2006; Goldstein BI, Bukstein OG. Comorbid substance use disorders among youth with bipolar disor­der: opportunities for early identification and prevention. J Clin Psychiatry Dec 1, 2009. [Epub ahead of print]; Goldstein TR et al: Dialectical behavior therapy for adolescents with bipolar disorder: a 1-year open trial. J Am Acad Child Adolesc Psychiatry 46:820, 2007; Hasin D et al: Effects of major depression on remission and relapse of sub­stance dependence. Arch Gen Psychiatry 59:375, 2002; Lynch TR et al: Mechanisms of change in dialectical behav­ior therapy: theoretical and empirical observations. J Clin Psychol 62:459, 2006; Ostacher MJ et al for STEP-BD Investigators: Impact of substance use disorders on recovery from episodes of depression in bipolar disorder pa­tients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry [Epub ahead of print]; Rizvi SL, Linehan MM: Dialectical behavior therapy for personality disorders. Curr Psychiatry Rep 3:64, 2001; Salloum IM et al: Efficacy of valproate maintenance in patients with bipolar disor­der and alcoholism: a double-blind placebo-controlled study. Arch Gen Psychiatry 62:37, 2005; Sherwood Brown E et al: A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence. Alcohol Clin Exp Res 33:1863, 2009; West AE, Pavuluri MN: Psychosocial treatments for childhood and adolescent bipolar disorder. Child Adolesc Psychiatr Clin N Am 18:471, 2009.