1. Antidepressants, Anxiolytics, and Sedative/Hypnotics

2. Antidepressants Tricyclic Antidepressants (TCAs) Monoamine Oxidase Inhibitors (MAOIs) Selective Serotonin Reuptake Inhibitors (SSRIs) Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Atypical antidepressants Atypical antipsychotics

3. Depression Depressed mood, loss of pleasure or interest in usual activities Sustained over time Subtypes –Major depression –Clinical depression –Subclinical depression –Post-partum –Bereavement

4. Depression Every patient in the hospital needs to have depression addressed –Loss of functionality –Loss of youth/feeling of control –Chronic illness –Altered sleep and exercise patterns\ –Altered role

5. Depression Treatment Cognitive therapy Behavioral therapy (exercise, art, etc.) ECT Pharmacology –Older protocol: treat major depression 6 – 12 months –Newer: long term or lifelong therapy –Distinguish: situational/transient depression

6. TCAs Old drugs, cheap Multiple actions unsure –Inhibition of Norepinephrine & Serotonin reuptake Multiple side effects Not effective for depression except at high doses May be toxic before becomes effective Often used as adjunct for sleep and pain

7. Adverse Effects Orthostatic hypotension Anticholinergic effects Diaphoresis Sedation Cardiac toxicity Seizures Hypomania

8. TCA Treatment Must start low  avoid toxicity –Takes several weeks to achieve effect –Starting high does not decrease time Selecting a drug –Most are dosed once daily, usually HS –Choosing your side effects More sedating drugs for patients with insomnia, etc. –Common agents: amitriptyline, nortriptyline, imipramine

9. MAOIs Older drugs Relatively effective, but high toxicity –Especially drug and food interactions Considered third line therapy Hypertensive crisis –When using MAOIs, avoid Avocadoes, cheese, wine, beer, soups, soy sauce, chocolate, caffeine, smoked foods Yeah… no wonder they’re depressed Linezolid (Zyvox): MAOI features

10. SSRIs Relatively new (1987) Most prescribed class for depression Blocks reuptake of serotonin only –Take 2 – 3 weeks for therapeutic effect Uses: –Depression –Anxiety –Social phobia, obsessive-compulsive, PDD

11. Adverse Effects Sexual dysfunction Weight gain Serotonin syndrome: 2 – 72 hours Withdrawal Syndrome Teen suicide? My experience with patients: –“feel flat,” “feel unresponsive” –Disturbing dreams

12. Agents Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Fluvoxamine (Luvox) Citalopram (Celexa) Escitalopram (Lexapro) (left hand of citalopram)

13. Teaching Points Therapeutic delay Warning signs of Serotonin Syndrome Withdrawal syndrome Sexual side effects

14. SNRIs Venlafaxine (Effexor) – NE & serotonin reuptake inhibitor (weak dopamine); causes mild excitation Duloxetine (Cymbalta)

15. Atypical Antidepressants Bupoprion (Wellbutrin) Nefazadone (Serzone) – multiple effects Mirtazapine (Remeron) – new class of drug; increased release of NE and serotonin

16. Bupoprion (Wellbutrin) Unclear action, but definitely blocks something with Dopamine May increase sexual desire May cause excitation Dopamine associated with addictive behaviors –Bupoprion marketed for smoking cessation (Zyban) –Also may help concentration  ADD

17. Atypical Antipsychotics Are not used for depression alone –Potentiate other antidepressant drugs –Used for depression with psychotic features Common agents –Clozapine (Clozaril) –Risperidone (Risperdal) –Olanzapine (Zyprexa) –Quetiapine (Seroquel)

18. Sedative-Hypnotics Benzodiazepines Benzo-like Barbiturates Miscellaneous

19. Benzodiazepines Safer and lower abuse potential that other CNS depressants (barbiturates) Mechanism –Potentiate GABA (CNS neurotransmitter) –Bind to GABA-chloride gate receptors and enhance the natural action of GABA –Finite action All are controlled substances

20. Benzodiazepines Effects –CNS Reduce anxiety Promote sleep Muscle relaxation Anterograde amnesia –CV: PO none; IV hypotension, cardiac arrest –Resp: weak depressants alone

21. Kinetics Most well absorbed PO Metabolism –Most have active metabolites –Duration is wildly different among agents –Example Flurazepam: 2-3 hour half-life; metabolite 50 hours

22. Benzo Uses Anxiety Insomnia Seizure Muscle Spasm Alcohol withdrawal (DT prevention) Panic Disorder Surgery –Induction of anesthesia –Conscious sedation

23. Adverse Effects CNS: drowsy, lightheaded, concentration, MVA Amnesia Paradoxical effects Resp depression Abuse Don’t use in pregnant women

24. Common Benzos Diazepam (Valium) Lorazapam (Ativan) Alprazolam (Xanax) Clonazepam (Klonopin) Chlordiazepoxide (Librium) Temazepam (Restoril) Midazolam (Versed) – conscious sedation

25. Benzo-like Unrelated to Benzo chemical structure, but upregulate GABA in a similar manner Schedule IV drugs –Zolpidem (Ambien) Middle of the night confusion –Zaleplon (Sonata) Better for falling asleep, not staying asleep

26. Barbiturates Bind to GABA-chloride receptor –Directly activate receptor –Enhance GABA’s natural action –No ceiling on effect Highly addictive Therapeutic uses for –Seizure –Anesthesia induction Common: Phenobarbital

27. Other Sedative-Hypnotics Antidepressants –Amitriptyline (Elavil) –Trazadone 1 st generation antihistamine –Diphenhydramine (Benadryl, Nytol, Sominex) –Doxylamine (Unisom) –Hydroxyzine (Atarax)

28. Anxiety Benzos, SSRIs, others –Generalized Anxiety Disorder –Situational anxiety SSRIs –Panic disorder –Obsessive-Compulsive D/O –Social anxiety –PTSD

29. Other Anxiolytics Buspirone (Buspar) –No sedation –No abuse potential –No interaction with ETOH –BUT, develops slowly: at least a week –Takes several to reach full potential –Used for short term therapy (up to a year) Beta blockers –Primarily for performance/test anxiety

30. Vitamin H: The Abused Antipsychotic Haloperidol (Haldol) –Often prescribed by physicians for inpatient “agitation” –“ICU psychosis” –Haldol is not a sedative. Should not be used as either a sedative nor anxiolytic –If giving it more than twice a day CALL THE PHYSICIAN AND GET ANOTHER DRUG ORDERED!!!!!!