www.mghcme.org

Mood Disorders

Shamim Nejad, MD

Medical Director, Psycho-Oncology Services

Swedish Cancer Institute

Swedish Medical Center

Seattle, Washington

Shamim.Nejad@swedish.org

www.mghcme.org

Disclosures

“Neither I nor my spouse/partner has a relevant financial relationship with a commercial interest

to disclose.”

www.mghcme.org

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)

www.mghcme.org

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.”

www.mghcme.org

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

www.mghcme.org

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.

www.mghcme.org

www.mghcme.org

Management of Depression and SUD

Greenfield SF, et al.. Archives of General Psychiatry. 1998; 55:259–65.

www.mghcme.org

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: 0.18-0.58)

– Heterogeneity significant (p<0.02)

www.mghcme.org

Management of Depression and SUD

(Nunes and Levin, 2004)

www.mghcme.org

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: 0.18-0.58) – 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

www.mghcme.org

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)

www.mghcme.org

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

www.mghcme.org

• 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

Management of Depression and SUD

www.mghcme.org

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

www.mghcme.org

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

www.mghcme.org

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

www.mghcme.org

• 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

www.mghcme.org

19

• 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 300-600mg at a time • Target level between 0.5-1.0 meq/L

Management of BMD and SUD

www.mghcme.org

Other AEDs

• Valproate – 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

• 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

www.mghcme.org

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

www.mghcme.org

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

www.mghcme.org

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; 27:307-312. Schmitz J et al. Addict Disord Treat 2002; 1:17-24. Devido JJ & Weiss RD, Curr Psychiatry Rep. 2012; 14(6): 610–618