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Manic episodes and drug abuse – diagnosis and treatment

Manic episodes and drug abuse – diagnosis and treatment. Dr.Paola Rosca Head- Dept. for the Treatment of Substance Abuse December 17, 2012. BIPOLAR DISORDERS AND DRUG ABUSE. Bi-polar spectrum disorders and addiction often co-occur They are reciprocal risk factors

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Manic episodes and drug abuse – diagnosis and treatment

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  1. Manic episodes and drug abuse – diagnosis and treatment Dr.PaolaRosca Head- Dept. for the Treatment of Substance Abuse December17, 2012

  2. BIPOLAR DISORDERS AND DRUG ABUSE • Bi-polar spectrum disorders and addiction often co-occur • They are reciprocal risk factors • Subjects falling in the bipolar spectrum have increased risk for substance abuse and move towards addiction • Frequently misdiagnosed especially in milder forms • The use of opioid agonists in heroin addicts with bipolar disorder has proved to be mood stabilizing and with combined mood stabilizing drugs it reaches best therapeutic effects • MaremmaniI,PerugiG,PaciniM,Akiskal HS, J Affect Dis, 2006, 93(1-3):1-12.

  3. Cocaine Abuse and Bipolar Spectrum • Specific relationship between bi-polar disorder and stimulant abuse • It has been assumed that cocaine use is intended to optimize hyperthymia, hypomania, cyclothymia. • It is frequently co-morbid with heroin addiction • A study on 1090 heroin addicts in treatment between 1994-2005, aged 29+-6 , 76% males showed a link between current cocaine abuse and double pathology, with special relevance to the bipolar spectrum, and psychotic disorders • Possible model linking bipolarity and cocaine • Sub-threshold bi-polarity seems to predispose to heroin addiction

  4. Cocaine Abuse and Bipolar Spectrum • Craving for the suppressed hypomania could lead to cocaine abuse • Unmasking of frank bipolar disorder- mixed states, severe mania, and psychotic states • Further research needed MaremmaniI, Pacini M, Perugi G et al, J Affect Dis,2008;106(1-2):55-61.

  5. SUD AND YOUTH ONSET BIPOLAR DISORDER • Co-morbid bipolar disorder and cannabis use is well known among adults • Youth-onset bi-polar disorder confers higher risk of SUD compared with adults • Bipolar disorder precede SUD in 55-83% of cases • Opportunity for prevention: screening for SUD in bipolar youth since the age of 10 • Education and family intervention • Preventive intervention has been found successful • Goldstein BI, Bukstein OG, J Clin Psych, 2010; 71(3):348-58.

  6. ADOLESCENT SUD AND BD • Study conducted on 211 offspring aged 12> with one BD parent • Lifetime SUD in24% offspring • Cannabis use the most common • Peak hazard of SUD 14-20 years of age • Male sex, previous mood disorder, parental history of SUD contributed to the risk of SUD in the offspring • SUD predicted increased risk of psychosis • The estimated hazard of a major psychosis in SUD youth was 3 fold • Duffy A, Horrocks J, Milin R et al, J Affect Dis,2012;142(1-3):57-64.

  7. Clinical outcomes in BD patients with cannabis use • The study compared clinical outcomes and neuro-cognitive functions of BD I patients with and without cannabis use • RETROSPECTIVE STUDY OF A LARGE COHORT- 200 PATIENTS • The Cannabis group had more males, and a higher proportion of psychosis • Interestingly they showed better neuro-cognitive performance but poorer prognosis Braga RG,BurdickKE,Derosse P et al, Psychiatry Res,2012;200(2-3):242-245.

  8. Alcohol and Cannabis use and age of onset of BD • Cannabis use coincided with previous manic or hypo-manic episodes while alcohol with previous depressive episodes • Cannabis use is also associated with the development of manic symptoms and lifetime cannabis use is associated with 5 fold increase in BD. • Patients with alcohol use had a significant later onset of BD and were similar to non-users. • Family history of affective or psychotic disorders was higher in cannabis users

  9. Alcohol and Cannabis use and age of onset of BD • Alcohol users had lower rates of other substances abuse than cannabis users • In cannabis users the use of cannabis generally preceded the onset of BD while in alcohol users the opposite was true. • Early onset of BD is associated with higher risk for cannabis use. • There seems to exist a common genetic pathway for cannabis use and BD. LagerbergTV,Sundet K, Aminoff SR et al, 2001; Eur Arch Psych Clin Neurosci;261(6):397-405.

  10. CANMAT Task Force Recommendations for mood disorders and comorbid substance use • Bipolar disorders are frequently associated with SUDs. • Therapeutic efficacy may differ due to the presence of SUD • THE NEED TO PROVIDE GUIDANCE TO CLINICIANS • First choice recommendations were possible only for alcohol, cannabis, and cocaine with bipolar disorder • Psychotherapies were considered an essential component of the overall treatment of comorbid SUD and Bipolar Disorder Beaulieu S, Saury S, Sareen J et al, 2012, Am J Clin Psych;24(1):38-51.

  11. Michael’s Case: Introduction • 22-year-old man, in good general physical health • Presents with a 7-10 day history of decreased need for sleep (5 hours), restlessness, and difficulty concentrating • In office, found to be somewhat agitated, impatient, rude (unusual for him) • No current medications • Drinks alcohol socially; occasional THC use • Usually gets along well with others, has no history of impulsivity and has a steady circle of friends. • 2 years ago had an episode of depression that lasted for 3 months, with no apparent precipitating event • Family history: alcoholic father with history of depression, impulsivity, grandiosity, and aggression Scientific Committee. 2010.

  12. What supplemental information would you ask for at this stage? • How bad is your sleep? • How low has your mood become? • Any suicidal ideations? • How bad is your concentration/attention? • Is your mood variable throughout the day? • Investigate both the depression and the mania • Substance abuse – has patient’s THC consumption increased? • Assess functionality • Evaluate if they can maintain a relationship • Look at environmental stressors • Check thyroid Das AK et al. JAMA. 2005;293(8):956-963. Ebmeier KP. Practitioner. 2010;254(1729):19-22, 12. Scientific Committee. 2010. Yatham LN et al. Bipolar Disord. 2005;7 Suppl 3:5-69.

  13. Diagnostic Challenges • Psychotic symptoms are common in bipolar disorder • 58% by clinical evaluation • 90% by self-report • More common in mania than in depression APA. Am J Psychiatry. 2002;159(4 Suppl):1-50. Zarate CA. J Clin Psychiatry. 2000;61 Suppl 8:52-61; discussion 62-53.

  14. 69% Misdiagnosed Misdiagnosis of Bipolar Disorder • Patients were incorrectly diagnosed with: • Unipolar depression 60% • Anxiety disorders 26% • Schizophrenia 18% • Borderline or antisocial PD 17% • Alcohol abuse/dependence 14% Hirschfeld RM et al. J Clin Psychiatry. 2003;64(2):161-174.

  15. Medical Comorbidities of Bipolar Disorder 11.8% Current alcohol abuse (n = 2154) 32.2% Past alcohol abuse (n = 2154) 31.2% Smoking (n = 1000) Past drug abuse (n = 2154) 21.7% 7.3% Current drug abuse (n = 2154) 31.9% Anxiety disorders (n = 1000) 9.5% ADHD (n = 1000) 0 10 20 30 40 50 60 70 Prevalence (%) Parikh SV, et al. Can J Psychiatry. 2010;55(3):33-40. Weiss RD, et al. J Clin Psychiatry. 2005;66(6):730-735; quiz 808-739. 15

  16. Medical Comorbidities of Bipolar Disorder • Neuroendocrine abnormalities • Affect on corticotropin-releasing hormone (CRH), cortisol levels, and glucocorticoid receptor (GR) function • Cardiovascular disease • Patients display an increase in cardiovascular risk factors (smoking, diabetes, hypertension, dyslipidemia, and obesity) • Obesity • 31-36% overweight; 26-34% obese • Asthma, COPD, emphysema • smoking is prevalent among bipolar patients • Compromised immune response • Dendritic cells aberrancies and decrease in lymphocytes • Seizure disorders • Migraine headaches Abeer et al. Egypt J Immunol. 2006;13(1):79-85. Knijff EM et al. Biol Psychiatry. 2006;59(4):317-326. Mula M et al. Expert Rev Neurother. 2010;10(1):13-23. Murray DP et al. Curr Psychiatry Rep. 2009;11(6):475-480. Watson S et al. Br J Psychiatry. 2004;184:496-502.

  17. Obstacles to Management and Treatment • Diagnostic confusion • Patients more likely to seek treatment for depressive than manic symptoms • Frequent comorbid substance abuse • Patient denial, fear of stigma, impaired insight • Clinician’s reluctance to use stigmatizing diagnosis • Inconsistent adherence with treatment recommendations • Previous treatment misadventures Hirschfeld RMA, et al. J Clin Psychiatry. 2001;62 Suppl 14:5-9. Manning JS. Prim Care Companion J Clin Psychiatry. 2002;4(4):142-150. Shah NN, et al. Psychiatr Q. 2004;75(2):183-196. Young RC, et al. Br J Psychiatry. 1978;133:429-435.

  18. PHARMACOLOGICAL TREATMENT • Double pathology including Bipolar Disorder and SUD should be treated with atypical anti-psychotics in the acute manic phase • It is suggested to add a mood-stabilizing agent’ which is also effective in preventing craving for substance abuse.

  19. Agents RecoAAAAAmmended for Acute Mania Yatham LN et al. Bipolar Disord. 2009;11(3):225-255.

  20. Treatment Algorithm for Acute Mania Start a 1st line agent for mania Appropriately dose for 2 weeks as an initial trial period Monitor response Continue therapy Adjust dose Consider switching Add another agent Yatham LN et al. Bipolar Disord. 2009;11(3):225-255.

  21. Alphabetical List of Medications by Generic Name Generic name (Trade name) Atypical antipsychotics aripiprazole (Abilify) asenapine (Saphris) clozapine (Clozaril) olanzapine (Zyprexa) paliperidone (Invega) quetiapine (Seroquel) risperidone (Risperdal) ziprasidone (Zeldox)

  22. What Additional Issues Should be Considered? • Akathisia • Inner restlessness associated with an urge to move • Risk factors: use of typical vs atypical antipsychotic agents, rapid dose escalation, higher doses, switching • Made worse by increased dose of antipsychotic • Agitation • Unpleasant state of extreme arousal, increased tension, and irritability • Made better by increased dose of antipsychotic • Activation • Stimulation of neural and symptomatic response • Anxiety • Both a psychological and physiological state • Characterized by an unpleasant feeling; typically tension, uneasiness, fear, or worry Day RK. J Affect Dis. 1999;55(2-3):89-98. Dressler D et al. J Neurol. 2005;252(11):1299-1306. Taylor D et al. In: The Maudsley Prescribing Guidelines. 2007.

  23. Significance of Weight Gain “…Obesity has become an equal, if not greater, contributor to the burden of disease than smoking.” Jia H, et al. Am J Prev Med. 2010;38(2):138-44. Weight change in treatment-naive patients with a mood disorder Jia H et al. Am J Prev Med. 2010;38(2):138-144. Taylor VH et al. J Affect Disord. 2008;109(1-2):127-131.

  24. Metabolic Risk of Atypical Antipsychotics ** Data suggest that quetiapine, like other atypical antipsychotics such as olanzapine, can cause clinically meaningful increases in insulin resistance, which may lead to new or exacerbated cases of type 2 diabetes. Fagiolini A et al. Curr Psychiatry Rep. 2007;9(6):521-528. Newcomer JW. Am J Manag Care. 2007;13(7 Suppl):S170-177. Yatham LN et al. Bipolar Disord. 2009;11(3):225-255. 24

  25. Extrapyramidal Side Effects Tardive dyskinesia Dystonic reactions Extrapyramidal side effects Akathisia Pseudoparkinsonism Taylor D et al. In: The Maudsley Prescribing Guidelines. 2007. 25

  26. Side Effect Profiles Moderate risk High risk Neutral - Low risk EPS: extrapyramidal side effects Harrigan EP et al. J Clin Psychopharmacol. 2004;24(1):62-69. Keck PE et al. J Clin Psychiatry. 2006;67(4):626-637. Kim B et al. J Affect Disord. 2008;105(1-3):45-52. Miller D et al. J Clin Psychiatry. 2001;62(12):975-980. Olfson M, et al. Am J Psychiatry. 2006;163(10):1821-1825. Yatham LN et al. Bipolar Disord. 2009;11(3):225-255. 26

  27. Prolactin-Related Adverse Effects * * Henderson DC et al.J Clin Psychiatry. 2008;69 Suppl 1:32-44.

  28. Evolution of Antipsychotic Medications chlorpromazine haloperidol clozapine risperidone olanzapine paliperidone quetiapine ziprasidone aripiprazole Miyamoto S et al. Mol Psychiatry. 2005;10(1):79-104. Shapiro DA et al. Neuropsychopharmacology. 2003;28(8):1400-1411. 28

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