www.mghcme.org Mood Disorders Shamim Nejad, MD Director, Adult Burns & Trauma Psychiatry Division of Psychiatry and Medicine Medical Director, Addiction Consultation Team MGH Center for Addiction Medicine Massachusetts General Hospital Assistant Professor of Psychiatry Harvard Medical School [email protected]
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www.mghcme.org
Mood Disorders
Shamim Nejad, MD Director, Adult Burns & Trauma Psychiatry Division of Psychiatry and Medicine Medical Director, Addiction Consultation Team MGH Center for Addiction Medicine Massachusetts General Hospital Assistant Professor of Psychiatry Harvard Medical School [email protected]
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Disclosures
“Neither I nor my spouse/partner has a relevant financial relationship with a commercial interest
to disclose.”
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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%
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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.”
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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
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Relationships Between Co-Occurring Mood Symptoms and SUDs
Relationship Mechanism Clinical Implications
Substance use causes mood symptoms Use, intoxication, withdrawal or neuropsychiatric sequelae of chronic use
SUD is chronologically primary; mood symptoms resolve with abstinence or reduced substance use; treatment focused on substance use
Substance use causes mood symptoms which worsen over time
Loss in multiple spheres lead to demoralization and depression; physiologic effects from chronic use lead to vulnerability to mood symptoms
Mood symptoms follow SUD but persist after abstinence; will need to treat both mood and SUD’s.
Mood symptoms lead to substance use Using substances to relieve symptoms of mood symptoms - ‘self-medication’
Mood symptoms are primary or emerge during abstinence, preceding relapse; pure ‘self-medication’ is rare
Substance use is associated with increased disinhibition and impulsivity from hypomania/mania
Disinhibition/impulsivity Substance use is secondary to mood symptoms; pure ‘self-medication’ is rare
Mood symptoms cause substance use which then worsens over time
Exposure to substances during episode of mood disorder induces vulnerability to SUD
Substance use is secondary but persists after mood disorder is treated; treat both conditions
Independent disorders Both mood disorders and SUD are present in general population with increased comorbidity
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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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
– Comorbid 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
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• 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*
– Trazodone
• Tricyclics (TCAs) – E.g., nortriptyline, amitriptyline, imipramine, clomipramine
* Brand name only
Management of Depression and SUD
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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
Management of Depression and SUD
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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
Management of Depression and SUD
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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
Management of BMD and SUD
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• 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;11:465-71.
Management of BMD and SUD
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• 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
Management of BMD and SUD
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Initiating a Mood Stabilizer
• Get baseline creatinine and TSH
• Lithium- start with 300mg BID
• Check level in a week • Titrate up by 300-
600mg at a time • Target level between
0.5-1.0 meq/L
• Obtain baseline LFTs and CBC with differential
• Valproate- start with 250mg BID
• Check level in a week
• Titrate up by 250-500mg at a time
• Target level is between 50-100 mcg/mL
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Management of BMD and SUD
• Lithium (cont.)
– If the patient has any of the following features they may not respond well to Lithium: • Borderline features
• Rapid cycling
• Mixed episodes
• Depression proceeds mania
• Substance use
– With these patients anti-epileptic drugs (AEDs) are a good choice
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Other AEDs
• 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
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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
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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
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Management of BMD and SUD
• Behavioral approaches
– Integrated group therapy
– Cognitive-behavioral therapy
Weiss RD, J Subst Abuse Treat 2004; 27:307-312. Schmitz J et al. Addict Disord Treat 2002; 1:17-24.
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