DepressionIbrahim Sales, Pharm.D.Associate Professor of Clinical PharmacyKing Saud Universityisales@ksu.edu.sa

What is a Major Depressive Episode?• Depressed mood and SIG-E-CAPS criteria• S: Suicidal ideation• I: decreased Interests• G: excessive Guilt (worthlessness, hopelessness)• E: decreased Energy• C: decreased Concentration• A: Appetite changes• P: Psychomotor retardation or agitation• S: Sleep disturbance

What is a Major Depressive Episode?• Must last at least 2 weeks• At least 5 of the criteria with one including depressed mood or

decreased interests• Must cause clinically significant impairment

Hamilton Depression Scale

Therapeutic Goals• Eliminate or significantly reduce symptoms. Remission

(symptom-free or nearly symptom-free) should be the goal of treatment of depression, although a majority of patients continue with residual symptoms

• Restore functioning to premorbid levels• Prevent depressive relapse.• Minimize medication side effects.• Ensure adherence with the prescribed regimen

Drug Classes for Depression• Selective Serotonin Reuptake Inhibitors (SSRI)• Serotonin & Norepinephrine Reuptake Inhibitor (SNRI)• Tricyclic antidepressants (TCA)• Monoamine Oxidase Inhibitors (MAOI)• Others• Bupropion, Mirtazapine• Nefazodone, Trazodone

Response Rates

• Pharmacotherapy: Response in 50-60% of adults• 1-4 weeks for any effect (sleep sooner)• 6-12 weeks for substantial benefit• Remission in 30%

• Psychotherapy is as effective as drugs• Cognitive Behavior Therapy (CBT)

• Electroconvulsive therapy (ECT)• 80-90% effective• 50% in those failing pharmacotherapy

SSRI’s• First line drugs (replaced TCA, MAOI)• Similar efficacy; variable individual response• Citalopram (Celexa)• Escitalopram (Lexapro)• Fluoxetine (Prozac, Prozac Weekly, Generic)

• Long half-life, CYP 450• Paroxetine (Paxil, Paxil CR)

• CYP 450• Sertraline (Zoloft)

Adverse effects of SSRI’s• Nervousness, insomnia• Start at low dose & titrate

• Nausea, Diarrhea, headache, fatigue• Sexual dysfunction• add sildenafil or bupropion

• Withdrawal with abrupt discontinuation• Nervousness, anxiety,

irritability…

• Long term weight gain• Serotonin syndrome

especially in overdose• Drug interactions CYP

450• Fluoxetine, Paroxetine

• Pregnancy• Children

SNRI’s• Side effects like SSRI and increase blood pressure with high dose. More

dangerous in overdose.• Venlafaxine (Effexor, Effexor XR)

• Meta-analysis found more effective than SSRI• Desvenlafaxine• Active metabolite, not better

• Duloxetine (Cymbalta) • More effective than placebo and inadequately dosed SSRI• Useful also for concomitant neuropathic pain• Diabetic neuropathy & Fibromyalgia

• Caution with liver disease

TCA’s & MAOI’s

• Tricyclic (TCA)Dangerous in overdose. Anticholinergic (urinary retention, constipation, dry mouth, blurred vision), orthostatic hypotension, weight gain, sedation, sexual dysfunction• Amitriptyline (Generic, Elavil)• Desipramine (Generic, Norpramin)• Nortriptyline (Generic, Pamelor)

• MAOIs dangerous / lethal drug interactions!• Phenelzine (Nardil) & Tranylcypromine (Parnate)

Other drugs• Depression with concurrent insomnia or agitation (i.e. use sedating

agents)• Mirtazapine (Remeron, Remeron SolTab)

• Rare neutropenia; increase appetite, dizziness, dry mouth• Nefazodone (Serzone)

• Rare hepatic failure; nausea, dizziness, dry mouth• Trazodone (Desyrel, Desyrel Dividose)

• Adjunct for treatment of SSRI – induced insomnia; priapism

Alternatives• If intolerant of SSRI, SNRI

i.e. due to sexual dysfunction, weight gain, sedation• Bupropion (Wellbutrin, Wellbutrin SR)

• Agitation, anxiety, insomnia, hypersensitivity,• Seizures, Contraindicated in anorexia-bulimia

• Electroconvulsive Therapy (ECT)• Effective and Safe• Use when drugs not tolerated

Second Line• Alternatives if unresponsive to SSRI, SNRI• Switch to another antidepressant

• Same class or another class• Combine with another class (Bupropion)• Add Atypical antipsychotic for “augmentation”

• Aripiprazole, Quetiapine, Olanzapine

Stepwise ApproachSSIR, SNRI or other (MRT, BUP)

Add psychotherapyAt any time

Partial or no response at 4-6 weeks at adequate dose

Reassessdiagnosis

Inadequate Response

Switch to new antidepressants from different classes

Augment with1 Lithium2 Atypical antipsychotic3 Lamotrigine4 Thyroid hormone

Combine two antidepressants from different classes

Consider ECT at any time, especially ifVery severe, not eating, catatonia, psychotic, suicidal, pregnant

Patient Counseling

• Works to increase levels of chemicals in your brain• Not addictive• Must be taken daily NOT PRN• Takes several weeks to see effects• Should be taken for 6-12 months• Common ADE• Be alert to symptoms of worsening depression

and suicidality