1. Depression Ibrahim Sales, Pharm.D. Associate Professor of Clinical Pharmacy King Saud University isales@ksu.edu.sa

2. 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

3. 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

4. Hamilton Depression Scale

5. 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

6. 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

7. 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

8. 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)

10. 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

11. 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

13. 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)

15. 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

16. 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

18. 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

19. Stepwise Approach SSIR, SNRI or other (MRT, BUP) Add psychotherapy At any time Partial or no response at 4-6 weeks at adequate dose Reassess diagnosis Inadequate Response Switch to new antidepressants from different classes Augment with 1 Lithium 2 Atypical antipsychotic 3 Lamotrigine 4 Thyroid hormone Combine two antidepressants from different classes Consider ECT at any time, especially if Very severe, not eating, catatonia, psychotic, suicidal, pregnant

20. 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