Mood Disorders.

Transcription

1 Mood Disorders Shamim Nejad, MD Medical Director, Psycho-Oncology Services Swedish Cancer Institute Swedish Medical Center Seattle, Washington

2 Disclosures Neither I nor my spouse/partner has a relevant financial relationship with a commercial interest to disclose.

3 Epidemiology Lifetime prevalence of bipolar mood disorder is estimated to be 4.4% Lifetime prevalence of major depressive disorder is estimated to be 13.2% to 16.6% Lifetime prevalence of BMD with SUD is 47.3% (BMD I is 60.3%) Lifetime prevalence of MDD with AUD is 40.3% and with SUD is 17.2% National Epidemiologic Survey on Alcohol and Related Conditions (Conway et al., 2006)

4 Diagnostic Dilemma DSM criteria indicate: Mood disorder is primary if it is not due to the effects of alcohol or drugs. Mood disorder symptoms should have been present prior to the patient s substance problem and/or should persist during abstinent periods. All other occurrences of mood disorder symptoms, according to DSM, are likely substance induced.

5 DSM Criteria Independent Mood Disorder Mood symptoms preceded the onset of substance use Mood symptoms persist for a substantial period of time after cessation of acute withdrawal and severe intoxication Mood symptoms substantially in excess of what would be expected given the type or amount of the substance used or the duration of use Other evidence of an independent mood disorder Substance-Induced Mood Disorder Prominent and persistent disturbance in mood Mood symptoms develop during substance intoxication or withdrawal Mood symptoms are in excess of those usually associated with the intoxication or withdrawal syndrome Sufficiently severe to warrant independent clinical attention Not better accounted for by an independent mood disorder

6 Relationships Between Co-Occurring Mood Symptoms and SUDs Relationship Mechanism Clinical Implications Substance use causes mood symptoms Substance use causes mood symptoms which worsen over time Mood symptoms lead to substance use Substance use is associated with increased disinhibition and impulsivity from hypomania/mania Mood symptoms cause substance use which then worsens over time Independent disorders Use, intoxication, withdrawal or neuropsychiatric sequelae of chronic use Loss in multiple spheres lead to demoralization and depression; physiologic effects from chronic use lead to vulnerability to mood symptoms Using substances to relieve symptoms of mood symptoms - self-medication Disinhibition/impulsivity Exposure to substances during episode of mood disorder induces vulnerability to SUD Both mood disorders and SUD are present in general population with increased comorbidity SUD is chronologically primary; mood symptoms resolve with abstinence or reduced substance use; treatment focused on substance use Mood symptoms follow SUD but persist after abstinence; will need to treat both mood and SUD s. Mood symptoms are primary or emerge during abstinence, preceding relapse; pure self-medication is rare Substance use is secondary to mood symptoms; pure self-medication is rare Substance use is secondary but persists after mood disorder is treated; treat both conditions Each disorder persists during remission of the other; treat both disorders Adapted from Nunes and Weiss. Co-Occurring Addictive and Mood Disorders. The ASAM Principles of Addiction Medicine.

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8 Management of Depression and SUD Greenfield SF, et al.. Archives of General Psychiatry. 1998; 55:

9 Management of Depression and SUD 14 placebo-controlled trials of antidepressant medications DSM diagnosed patients with depression Alcohol, cocaine, opioids Hamilton Depression Scale (Ham-D) ES=0.38 (95% CI: ) Heterogeneity significant (p<0.02)

10 Management of Depression and SUD (Nunes and Levin, 2004)

11 Management of Depression and SUD 14 placebo-controlled trials of antidepressant medications DSM diagnosed patients with depression Alcohol, cocaine, opioids Hamilton Depression Scale (Ham-D) ES=0.38 (95% CI: ) Heterogeneity significant (p<0.02) Self-reported substance use outcome HamD ES > 0.5: Substance use ES=0.56 HamD ES < 0.5: Substance use ES was around 0 Remission or abstinence rates were low

12 Associations where antidepressant medications was effective versus not so much? Medication Effective Low placebo response Diagnosis of depression during abstinence No structured psychotherapy given Tricyclic or other noradrenergic medications used Medication Similar to Placebo High placebo response Diagnosis during active substance use Manual guided psychotherapy utilized Serotonin re-uptake inhibitor (Nunes and Levin, 2004)

13 Management of Depression and SUD When to consider pharmacotherapy: Prior positive responses to antidepressants Moderate to severe symptom burden: PHQ-9 scores > 10-14: consider antidepressants PHQ-9 scores > 15-19: antidepressants strongly encouraged PHQ-9 scores > 20-27: antidepressants usually a priority Past history of severe depression (hospitalizations, suicidality, protracted disability) Significant disturbance of sleep or appetite, or agitation Co-morbid condition that may benefit from antidepressants (e.g., chronic pain) Relevance of maintenance pharmacotherapy: prior history of recurrences and/or severity Patient preference Shared decision-making

14 Management of Depression and SUD Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine, paroxetine, sertraline, citalopram, escitalopram Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Venlafaxine, duloxetine, desvenlafaxine, levomilnacipran* Norepinephrine-Dopamine Reuptake Inhibitor (NDRI): Bupropion Miscellaneous Agents Mirtazapine Vilazodone* and vortioxetine* Tricyclics (TCAs) E.g., nortriptyline, amitriptyline, imipramine, clomipramine * Brand name only

15 Management of Depression and SUD Selecting an antidepressant Generic SSRIs, SNRIs, bupropion or mirtazapine are reasonable first line agents. No evidence for superiority of one agent or class for usual outpatient depression. Clinical considerations Prior good response/tolerability re-try same agent Depression with anxiety and/or irritability SSRI Severe depression and/or chronic pain SNRI Prominent weight loss, insomnia mirtazapine Problems with antidepressant sexual dysfunction bupropion or mirtazapine Motivated for smoking cessation bupropion Prior intermittent missed doses fluoxetine

16 Management of Depression and SUD The following agents are relatively less favorable first line agents when concerns exist about: Cytochrome P450 2D6 inhibition of metabolism of co-prescribed substrates (e.g., codeine, tamoxifen, TCAs, propranolol): X fluoxetine, paroxetine, duloxetine, bupropion Weight gain: X mirtazapine, paroxetine Drowsiness: X mirtazapine, paroxetine, trazodone Hypotension: X trazodone Hypertension: X SNRIs Seizure risk: X bupropion QTc prolongation: X citalopram, escitalopram Abrupt discontinuation-emergent reactions: X paroxetine, SNRIs

17 Management of BMD and SUD Generic name Trade name Manic Mixed Maintenance Depressed Valproate Depakote x x Carbamezapine ER x x Lamotrigine Lamictal Lithium x x x Aripiprazole Abilify x x x Ziprasidone Geodon x x x Risperdone Risperdal x x Asenapine Saphris x x Quetiapine Seroquel x x x Quetiapine XR Seroquel XR x x Chlorpromazine Thorazine x Olanzapine Zyprexa x x x Olanzapine fluoxetine comb Symbyax x

18 Management of BMD and SUD Lithium Only mood stabilizer shown to reduce suicide rate Rate of completed suicide ~15% Effective in long-term prophylaxis of both mania and depressive episodes in 70+% of BMD, I patients Factors predicting positive response to lithium Prior long-term response or family member with good response Classic pure mania Family history of BMD Obsessive features Mania is followed by depression Baldessarini R. CNS Spectr 2006;11:

19 Management of BMD and SUD Lithium (cont.) Side effects Weight gain Increased thirst, increased urination, water retention Nausea, diarrhea Tremor Cognitive dulling (mental sluggishness) Dermatologic conditions Hypothyroidism Birth defects Need to follow serum level Get baseline creatinine and TSH Lithium- start with 300mg BID Check level in a week Titrate up by mg at a time Target level between meq/l 19

20 Other AEDs Valproate Obtain baseline LFTs and CBC with differential Valproate- start with 250mg BID Check level in a week Titrate up by mg at a time Target level is between mcg/ml Carbamazepine Effect as a second line agent for mania prophylaxis Effective for therapy of depression in about 25% of patients Indicated for rapid cyclers, mixed patients. More complicated to use because of many drug-drug interactions Lamotrigine Indication similar to other AEDs

21 Other AEDs Lamotrigine Obtain baseline LFTs Start at 25mg X 2 weeks then titrate to 50mg X 2 weeks then increase to 100mg. From there you can titrate more quickly Initial titration should not be faster due to risk of Stevens Johnsons Syndrome/toxic epidermal necrolysis Caution with recent or concurrent use of valproate

22 Dopamine Antagonists Second generation medications: Risperidone Initiated at a dose of 1 to 2 mg once daily or in two divided doses The usual target dose is 4 to 8 mg/day Common side effects include hyperprolactinemia, akathisia, sedation, dyspepsia, nausea, and weight gain Aripiprizole Initiated at dose of 2.5 to 5mg once daily The usual target dose is 10-20mg taken once per day Common side effects include akathisia, headache, nausea, vomiting, constipation, insomnia Quetiapine Initiated at a dose of 50 to 100 mg once daily or in two divided doses The usual target dose is 200 to 800 mg taken at bedtime or in two divided doses Common side effects include headache, dry mouth, constipation, weight gain, sedation, dizziness, and orthostatic hypotension

23 Management of BMD and SUD Behavioral approaches Integrated group therapy Cognitive-behavioral therapy Motivational enhancement therapy Contingency management Weiss RD, J Subst Abuse Treat 2004; 27: Schmitz J et al. Addict Disord Treat 2002; 1: Devido JJ & Weiss RD, Curr Psychiatry Rep. 2012; 14(6):