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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 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 Outline • PIPC 1 – Introduction – PIPC Interview ® – MAPS-O – Mood Disorders – Suicide ® Outline • PIPC 2 – Anxiety Disorders • PIPC 3 – Neurotransmitters – The 3 Phases and the 5Rs – Medications – Cases and Discussion NEUROTRANSMITTERS Neurotransmitter Receptor Hypothesis of Antidepressant Action Decreased state due to upregulation of receptors 6-2 Stahl S M, Essential Psychopharmacology (2000) Neurotransmitter Receptor Hypothesis of Antidepressant Action Antidepressant blocks the reuptake pump, causing more NT to be in the synapse 6-5 6-6 Increase in NT causes receptors to down-regulate Stahl S M, Essential Psychopharmacology (2000) amount of NT receptor sensitivity clinical effect antidepressant introduced 6-1 Stahl S M, Essential Psychopharmacology (2000) The 3 Phases and 5 Rs • Acute • Response • Continuation • Remission • Maintenance • Relapse • Recovery • Recurrence EPISODE OF DEPRESSION RECOVERY OR REMISSION NORMAL MOOD DEPRESSION TIME 6 - 24 months 5-1 Stahl S M, Essential Psychopharmacology (2000) NORMAL MOOD REMISSION 100% RECOVERY DEPRESSION acute continuation maintenance 6 - 12 weeks 4-9 months 1 or more years TIME 5-3 Stahl S M, Essential Psychopharmacology (2000) NORMAL MOOD RELAPSE RECURRENCE DEPRESSION acute continuation maintenance 6 - 12 weeks 4-9 months 1 or more years TIME 5-4 Stahl S M, Essential Psychopharmacology (2000) 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 NORMAL MOOD RESPONSE RESPONSE DEPRESSION 5-2 Stahl S M, Essential Psychopharmacology (2000) 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 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 NORMAL MOOD RELAPSE RECURRENCE DEPRESSION acute continuation maintenance 6 - 12 weeks 4-9 months 1 or more years TIME 5-4 Stahl S M, Essential Psychopharmacology (2000) 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 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 NORMAL MOOD RELAPSE RECURRENCE DEPRESSION acute continuation maintenance 6 - 12 weeks 4-9 months 1 or more years TIME 5-4 Stahl S M, Essential Psychopharmacology (2000) MEDICATIONS General Considerations • Three Neurotransmitters – Serotonin – Norepinephrine – Dopamine • Three major sites of action – Reuptake pump – Post-synaptic receptor – MAO enzyme inhibition 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 Norepinephrine and Serotonin Reuptake Inhibitors: TCAD • Classic Tricyclic Antidepressants –amitriptyline (Elavil) –clomipramine (Anafranil) –desipramine (Norpramin) –imipramine (Tofranil) –nortriptyline (Pamelor) 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 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 Selective Serotonin Reuptake Inhibitors • Classic SSRIs –sertraline (Zoloft) –fluoxetine (Prozac) –paroxetine (Paxil) –citralopam (Celexa) 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 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 Less Selective Reuptake Inhibitors • Serotonin, Norepinephrine and mild Dopamine Reuptake Inhibitor –venlafaxine (Effexor) • Dopamine, Norepinephrine and mild Serotonin Reuptake Inhibitor –bupropion (Wellbutrin) 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 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 Postsynaptic Serotonin Inhibition • Serotonin (postsynaptic 5HT-2 inhibition) – trazodone (Desyrel) – nafazodone (Serzone) 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 CASES