1. PIPC ® Psychiatry In Primary Care Medications Robert K. Schneider, MD Departments of Psychiatry, Internal Medicine and Family Practice The Medical College of Virginia at the Virginia Commonwealth University Richmond, Virginia

2. PIPC ® Goals Effectively recognize, diagnose and treat mental illness in primary care Bring the psychiatry skills and knowledge base of the primary care physician on par with other medical specialty knowledge bases

3. Outline PIPC 1 –Introduction –PIPC ® Interview –MAPS-O ® –Mood Disorders –Suicide

4. Outline PIPC 2 –Anxiety Disorders PIPC 3 –Neurotransmitters –The 3 Phases and the 5Rs –Medications –Cases and Discussion

5. NEUROTRANSMITTERS

6. Decreased state due to up- regulation of receptors Neurotransmitter Receptor Hypothesis of Antidepressant Action 6-2 Stahl S M, Essential Psychopharmacology (2000)

7. 6-5 6-6 Stahl S M, Essential Psychopharmacology (2000) Antidepressant blocks the reuptake pump, causing more NT to be in the synapse Neurotransmitter Receptor Hypothesis of Antidepressant Action Increase in NT causes receptors to down-regulate

8. receptor sensitivity 6-1 Stahl S M, Essential Psychopharmacology (2000) amount of NT clinical effect antidepressant introduced

9. The 3 Phases and 5 Rs Acute Continuation Maintenance Response Remission Relapse Recovery Recurrence

10. DEPRESSION NORMAL MOOD RECOVERY OR REMISSION EPISODE OF DEPRESSION TIME 6 - 24 months 5-1 Stahl S M, Essential Psychopharmacology (2000)

11. acute 6 - 12 weeks continuation 4-9 months maintenance 1 or more years REMISSION RECOVERY DEPRESSION NORMAL MOOD 100% 5-3 Stahl S M, Essential Psychopharmacology (2000) TIME

12. 5-4 Stahl S M, Essential Psychopharmacology (2000) acute 6 - 12 weeks continuation 4-9 months maintenance 1 or more years TIME DEPRESSION NORMAL MOOD RELAPSE RECURRENCE

13. Acute Phase Treatment Focus is response and full remission establish target symptoms patient preference, “collaborative approach” Psychotherapy especially helpful in chronic depression or depression exacerbated by recent stressors Acute phase is over ONLY after a remission is achieved

14. DEPRESSION NORMAL MOOD RESPONSE 5-2 Stahl S M, Essential Psychopharmacology (2000)

15. Changing the Medication “Pseudoresistance” –Verifying Compliance (“like an antibiotic”) –“Too little, too late” –Inadequate duration –Correct diagnosis (undetected comorbid diagnosis) Worsening Condition –severity escalating –new symptoms developing (destructive impulses) Partial Remission vs. Full Remission

16. Continuation Phase Treatment Focus is to prevent relapse Period of time following full remission during which discontinuation of treatment will result in relapse Don’t stop before 6-9 months of therapy Don’t decrease the dosage Full Dosage, for the Full Period of Time

17. 5-4 Stahl S M, Essential Psychopharmacology (2000) acute 6 - 12 weeks continuation 4-9 months maintenance 1 or more years TIME DEPRESSION NORMAL MOOD RELAPSE RECURRENCE

18. Maintenance Phase Treatment Focus is to prevent recurrence Recurrence can only occur after the recovery from a previous episode Therefore only recurrent major depression is considered Maintain Full Dosage

19. Termination vs. Maintenance Degree of Functional Impairment Additional non-affective mental disorder Chronic medical disorder Prior history of depressive episode 1 episode: 50-80% 2 or more episodes: 80-90% Persistence of dysthymic symptoms

20. 5-4 Stahl S M, Essential Psychopharmacology (2000) acute 6 - 12 weeks continuation 4-9 months maintenance 1 or more years TIME DEPRESSION NORMAL MOOD RELAPSE RECURRENCE

21. MEDICATIONS

22. General Considerations Three Neurotransmitters –Serotonin –Norepinephrine –Dopamine Three major sites of action –Reuptake pump –Post-synaptic receptor –MAO enzyme inhibition

23. Common Classes TCAD –NE and 5HT Reuptake inhibition SSRI –5HT Reuptake inhibition “Less Selective” Reuptake inhibition –DA and NE (buproprion) –5HT and NE (venlafaxime) Post synaptic receptor blockade –Trazodone, nafazodone

24. Norepinephrine and Serotonin Reuptake Inhibitors: TCAD Classic Tricyclic Antidepressants –amitriptyline (Elavil) –clomipramine (Anafranil) –desipramine (Norpramin) –imipramine (Tofranil) –nortriptyline (Pamelor)

25. Norepinephrine and Serotonin Reuptake Inhibitors: Effects Primarily blocks reuptake of norepinephrine, serotonin and weakly dopamine Effective in severe depression and anxiety disorders Sedating properties, reduces pain and stimulates appetite Nortriptyline level is a meaningful measurement

26. Norepinephrine and Serotonin Reuptake Inhibitors Side Effects –urinary retention, constipation, blurred vision, dry mouth, weight gain, sexual dysfunction –orthostatic hypotension, delayed cardiac conduction Cautions –the elderly –cardiac patients

27. Selective Serotonin Reuptake Inhibitors Classic SSRIs –sertraline (Zoloft) –fluoxetine (Prozac) –paroxetine (Paxil) –citralopam (Celexa)

28. Selective Serotonin Reuptake Inhibitors: Effects Selectively blocks the serotonin reuptake pump Mild to moderate depression (max doses in severe) Safer in overdose Indicated for anxiety disorders

29. Selective Serotonin Reuptake Inhibitors: Side Effects Side Effects –nausea, headache –jitteriness and insomnia (especially early) –sexual dysfunction –“Discontinuation Syndrome” Cautions –very few –notable exception: Serotonin Syndrome

30. Less Selective Reuptake Inhibitors Serotonin, Norepinephrine and mild Dopamine Reuptake Inhibitor –venlafaxine (Effexor) Dopamine, Norepinephrine and mild Serotonin Reuptake Inhibitor –bupropion (Wellbutrin)

31. Serotonin, Norepinephrine & Mild Dopamine Reuptake Inhibitor venlafaxine (Effexor) –Effects blocks reuptake of serotonin, norepinephrine and dopamine (mildly) antidepressant effects and anxiolytic properties –Side Effects nausea, somnolence, dry mouth, constipation, nervousness, dizziness risk of increased blood pressure

32. Dopamine, Norepinephrine & Weak Serotonin Reuptake Inhibitor bupropion (Wellbutrin) –Effects moderate dopamine reuptake inhibition, norepinephrine reuptake inhibitor (bupropion metabolite), and weak serotonin reuptake inhibition antidepressant, antismoking, NOT ANXIOLYTIC –Side Effects agitation, tremor, insomnia, headache, constipation increased risk of seizures at doses above 450mg/day minimal sexual dysfunction, cardiac complications, or weight gain –Cautions history of seizures or previous head trauma

33. Postsynaptic Serotonin Inhibition Serotonin (postsynaptic 5HT-2 inhibition) –trazodone (Desyrel) –nafazodone (Serzone)

34. Postsynaptic Serotonin Inhibition trazodone (Desyrel) –Effects sedating, good hypnotic Post synaptic receptor blockade, weak SSRI –Side Effects difficult to get to high enough doses for depression sedation, dry mouth, orthostasis, priapism (very rare) nafazodone (Serzone) –Effects effective antidepressant good anxiolytic, effective in the anxious depressed Post synaptic blockade, moderate SSRI –Side Effects sedation (much less than trazodone), nausea, visual disturbances, lightheadedness

35. CASES