Bipolar Disorders. Disclosure Statement. I have no financial disclosures or conflicts of interest

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1 Bipolar Disorders Ahsan Naseem, MD Diplomate American Board of Psychiatry and Neurology Adult and Geriatric Psychiatry Medical Director Bryan Heartland Psychiatry Bryan Physician Network Partner Cheney Psychiatric Associates, LLC Disclosure Statement I have no financial disclosures or conflicts of interest 1

2 Learning Objectives 1. Screen and diagnose patients for bipolar disorder using validated tools. 2. Differentiate the etiology of mania type symptoms as primary bipolar disorder from secondary causes. 3. Categorize the management strategies for bipolar disorders based on the presenting phase: mania, hypomania, mixed state, depression, or maintenance or acute episodes. 4. Explain how the treatment for bipolar depression differs from other forms of depression. Introduction Episodic mood disorder with a progressive course characterized by hypomanic/manic episodes in conjunction with depressive episodes, interepisodic subsyndromal symptoms of mania, and/or depression (Judd et al. Arch Gen Psychiatry 2002) Due to its recurrent nature, patients are symptomatic 1/2 their lives (Judd et al. J Affect Disord 2003) Lifetime prevalence 0.6 1% for B1D and % for subthreshold BD (Merikangas et al. Arch Gen Psych 2011) 2

3 Case 1 44 year old male presenting with fatigue, increased irritability, interrupted sleep, severe reactivity over small stressors (i.e. chores at home, scheduled due assignments at work). Patient s spouse reports a decline in function where the patient is forgetful, increasingly disorganized. Patient has a family history of depression Harvard Med School, National Comorbidity Survey (NSC)

4 Harvard Med School, National Comorbidity Survey (NSC) 2017 Progression Typical trajectory of BD onset of sub threshold nonspecific symptoms in adolescence or early adulthood followed by emergence of threshold episode (Perugi et al. Compr Psychiatry 2000) Delay in onset of hypo/manic episodes and high prevalence of comorbid disorders contribute to high rate of misdiagnosis (Merikangas et al. Arch Gen Psychiatry 2011) 4

5 Case 2 24 year old university student presents with racing thoughts, impulsive behavior with increased spending and promiscuous sexual activity, reckless attitude towards classwork, poor sleep and a euphoric mood for the past 5 days. Her roommate reports the behaviors of sudden onset and on a bad day the patient experiencing visual hallucinations. Diagnosis of Mania and Depression: Mania Distinct period of abnormally and persistently elevated, expansive or irritable mood for at least 1 week accompanied by three of the following: High self-esteem Little need for sleep Increased rate of speech Flight of ideas Easy distractibility Increased interest in goals/activities Psychomotor agitation Increased risk-taking activities. Mixed Episodes Major Depression 2-week period and represents a change from previous function with five of the following: Depressed mood most of the day, nearly every day, by subjective report or observation Marked diminished interest Significant weight loss Insomnia or hypersomnia nearly every day Psychomotor retardation or agitation nearly every day Fatigue or loss of energy nearly every day Feelings of worthlessness or guilt Diminished ability to think or concentrate, indecisiveness nearly every day Recurrent thoughts of death, suicidal ideation DSM 5 5

6 Bipolar Diagnostic Categories Diagnosis Bipolar I disorder Bipolar II disorder Cyclothymic disorder Substance/medication induced bipolar and related disorders Bipolar and related disorders due to another medical condition Description At least 1 manic episode with/without episodes of hypomania or depression 1 hypomanic episode AND 1 major depressive episode in the absence of any lifetime history of mania 2 years (1 in children and adolescents) of hypomanic and depressive symptoms that fall short of meeting DSM criteria for either mood state Disturbance in mood that develops during or soon after substance intoxication or withdrawal Disturbance is directly a pathophysiological consequence of another medical condition Psychiatric Times Nov 20, 2015 Case 3 76 year old male, living independently, with established history of bipolar illness presents with acute confusion. He is brought in by his neighbor who reports the patient to be wandering, unable to answer straightforward questions; which is strongly unlike him. The neighbor brings in a bag of medicines which the patient might have been taking. 6

7 Key principles of pharmacotherapy of acute mania Goal: Treat symptoms of mania and control of associated behaviors Strength of evidence: Evidence for first line treatment of acute mania is considerable Monotherapy/combination therapy: Strong evidence for monotherapy in this phase of bipolar disorder Patients with psychotic features may benefit from short term antipsychotics Recommended pharmacotherapy Monotherapy: Lithium Valproate Atypical antipsychotic Combination therapy: Lithium or Valproate + Seroquel Lithium or Valproate + Olanzapine (Malhi et al, 2012) Key principles of pharmacotherapy of bipolar depression treatment Two common clinical presentations provide the context for psychopharm treatment of bipolar depression: i) New depressive episode (de novo bipolar depression) in the absence of prophylactic maintenance treatment with a mood stabilizer ii) Breakthrough episode occurs in context of ongoing mood stabilizing treatment 7

8 Strength of evidence Denovo depression: Overall, limited evidence as to which agents are efficacious Quetiapine monotherapy is supported by strong evidence Lamotrigine and carbamazepine are noted to be effective for bipolar depression Antidepressants may be of some utility in short term Breakthrough depression: Lamotrigine should be considered as an option for breakthrough episodes in patients with ongoing lithium treatment There is no evidence to support antidepressants in patients on a mood stabilizing agent; however, clinical experience suggests this as a second line option AES Question 8

9 AES Question Lithium pre initiation lab work includes which of the following as the highest priority? a. Serum prolactin b. Serum TSH c. Toxicology screen d. Serum SGPT and SGOT Recommended pharmacotherapy: De novo depression Monotherapy Quetiapine or Olanzapine Lamotrigine Combination therapy Li + Lamotrigine Mood stabilizer + antidepressant Recommended pharmacotherapy: Breakthrough depression Monotherapy N/A Combination therapy Li + Lamotrigine Mood stabilizer + antidepressant 9

10 Investigations for Safety Monitoring Baseline 3 months 12 months BP and thyroid function X X CBC with LFT X X Blood glucose and lipids X X X Prolactin X X Smoking and alcohol X X (Malhi et al 2012) Medications in Focus Lithium: Dosage range: Achieve therapeutic level mmol/l Av. delay in therapeutic effect is 2 3 weeks Narrow therapeutic index and severe toxicity Adequate hydration and awareness of drug drug interaction Common SE: weight gain, cognitive dullness, polyuria, polydipsia, GI Serious SE: renal problems (10 20%), hypothyroidism (5 35%) 10

11 Anticonvulsants Valproate: Maintain concentration range µg/ml (Allen et al. 1996) Common S/E: weight gain, tremor, osteoporosis, abnor LFTs, sedation Dangerous S/E: teratogenic in pregnant women, thrombocytopenia Wide therapeutic window but OD is dangerous (heart block and coma) Carbamazepine: Rare but potentially fatal S/E: blood dyscrasias, hypersensitivity reactions and cardiac conduction disturbances Common S/E: diplopia, blurred vision, nausea (dose dep and short lived) Anticonvulsants Lamotrigine: Dosage of 25 mg QD for 14 days then advancing to 50 mg QD during 3 rd to 4 th week. In the 5 th week, can be increased to 100 mg QD up to 200 mg into the 6 th to 6 th week. Relatively easy drug to administer but 10 14% will develop a benign rash when first prescribed. In contrast, a serious rash is extremely rare but can be lifethreatening. Should a rash appear, immediate discontinuation. Risk of rash increased when lamotrigine is combined with valproate. 11

12 Barriers to Practice Continuation of polypharmacy due to chronic history Lack of involvement of clinical pharmacy Limited communication with psychiatric providers Reliance on quick response agents such as BZDs Initiation of antidepressants with limited cover for mood stabilizers Adverse Lithium Carbamazepine Valproate Lamotrigine Effects Somnolence Cog Impair EPS + DD* + 0 Wt gain Dyslipid Thyroid Renal (Malhi et al 2012) 12

13 Barriers to Practice Long term management leads to noncompliance in estimated 60% of patients due to adverse effects (Semple D, Smyth R: Bipolar Illness 2009) Emphasis on efficacy and tolerability of agents Medicolegal and clinical risks in pregnancy, medical comorbidities Induction of manic symptoms with antidepressant care Risk of suicide: Lifetime attempts in bipolar patients 26 34% (Chen et al. Biol Psych 1996) More likely in depressed states 29% and mixed states 28% 10 15% of individuals will complete suicide (males, hx of past attempts, comorbid substance misuse) (Dalton et al. Bipolar Dis 2003) Key principles in treatment of mixed episode Strength of evidence: Many studies related to atypical antipsychotics, but limited in interpretability Haloperidol, atypical antipsychotics, carbamazepine and divalproex have been demonstrated to have equal efficacy for mixed states. The predominantly depressive state of bipolar disorder suggests lithium and lamotrigine may have a role in mixed episodes Monotherapy/combination therapy: Most individuals will require combination therapy, although combination treatments have not been robustly investigated in mixed states. Recommended pharmacotherapy Monotherapy Atypical antipsychotics Combination therapy Li or divalproex + atypical antipsychotic (Malhi et al 2012) 13

14 Best Practice Recommendations Diagnosis and differentiation between unipolar and bipolar depression will make paramount difference in treatment success Substance induced mood symptoms are common and need to be ruled out when high index of suspicion Mood stabilizers are the mainstay of treatment even when patients are presenting with bipolar depression Caution patients about side effects due to high prevalence and impact Use therapy based care, which can augment and expedite the recovery process 14