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Update in Clinical Psychopharmacology

Update in Clinical Psychopharmacology. Peter A. DeMaria, Jr., M.D., FASAM, DFAPA Tuttleman Counseling Services Temple University Clinical Professor of Psychiatry & Behavioral Sciences Temple University School of Medicine Philadelphia, PA. Disclosures.

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Update in Clinical Psychopharmacology

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  1. Update inClinical Psychopharmacology Peter A. DeMaria, Jr., M.D., FASAM, DFAPA Tuttleman Counseling Services Temple University Clinical Professor of Psychiatry & Behavioral Sciences Temple University School of Medicine Philadelphia, PA

  2. Disclosures • I am a treatment advocate for Reckitt-Benkiser Pharmaceutical Co.. • Use of trade versus generic drug names • Off-label use of drugs. • Role of counseling/psychotherapy Website: https://sites.google.com/site/achapsychopharmacology/

  3. Case A - Alisha Alisha is a 19 y/o sophomore student who presents for follow-up. A month ago she was diagnosed with major depression and started on citalopram 20 mg daily. She reports that she is tolerating the medication without side effects and has started to feel better but still has crying spells, difficulty with sleep low energy and is increasingly worried about completing her academically demanding schedule.

  4. Evaluating a Response to Antidepressant Medication • Is the patient taking it? • Ambivalence/stigma towards medication • Parental pressure to avoid medication • Availability (insurance, cost) • Is it the right: • Drug? • Dose? • Length of time? • Are there co-morbid conditions?

  5. Case A – Alisha (Part 2) Alisha reports that she got the medication and assures you that she has been compliant. You review the time course of response and recommend that she increase the dose to 40 mg to optimize her response to treatment. Additionally, you ask if she has been able to connect with the counseling center. She tells you that she has an intake appointment in the next week.

  6. Case A – Alisha (Part 3) (One month later; 2 months on citalopram) Alisha returns for her follow-up visit. She has been taking citalopram 40 mg daily and thinks it might be making her tired. She connected with a therapist at the counseling center and likes her. Alisha still reports decreased energy and feeling down. Her relationship with her partner has deteriorated and she is having thoughts of cutting herself. She denies SI.

  7. STAR*D • Largest (n=4041, age 18-75 y/o) study of treatment of non-psychotic MDD • Multiple real-world psychiatric and primary care settings • Conducted between July 2001 and April 2004 • Funded by National Institute of Mental Health (NIMH) • Goal was remission (< 5 on the QIDS-C16) • Treatment involved 6 levels with patient ability to choose options • Available at www.star-d.org

  8. STAR*D • MDD is a chronic and recurrent illness. • Using objective measurements of symptoms and side effects can help with treatment decisions. • Remission can take time (at least 8, but up to 14 weeks). • Many steps may be needed to reach remission. • Level 1 (citalopram @ 8 wks.): Remission = 37%, Response = 49% • Remission rate of 50% was reached after 2 steps. • Remission rate of 70% was reached after 4 steps • Remission results in better log-term outcomes. • Participant attrition is high. (Warden D et al. The STAR*D project results: a comprehensive review of findings. Current Psychiatry Reports 9:449-459, 2007.)

  9. Treatment Options for Non-Responsive MDD • Optimize dose and treatment time • Add psychotherapy • In-class switch (e.g. SSRI → SSRI) • Between class switch (e.g. SSRI → SNRI/other agent) • Augment • Brain stimulation

  10. Augmentation Strategies in Treating Major Depression • Add a second AD with a different MOA • L-Methylfolate (7.5 - 15 mg/day) • T3 (5 - 50 mcg) • Lithium • Atypical antipsychotic • Aripiprazole (2 – 15 mg/day) • Quetiapine XR (50 – 300 mg/day) • Supplements (?) • Omega-3-fatty acids • SAMe (1600 mg/day) • Creatine (5 gm/day)

  11. Vilazodone (Viibryd) • MOA: SSRI and partial5-HT1A agonist • Metabolism: P450 CYP 3A4 • FDA Approval: Major depression • Efficacy demonstrated compared to placebo; no head-to-head trial with other AD. Separates from placebo at one week (?). • Side effects: diarrhea. Insomnia, dizziness • Dosing: Start with 10 mg increase weekly to 20 mg then 40 mg. • Take with food • Benefits(?): low sexual dysfunction, no weight gain

  12. Focal Brain Stimulation • Vagal Nerve Stimulation (VNS) • Pulse generator implanted in the left chest wall • Electrode wrapped around the left vagus nerve • Pulse on for 30 seconds and off for 5 minutes • Efficacy = ? • Transcranial magnetic stimulation (TMS) • Uses an electromagnetic coil placed against the scalp to create a rapidly changing magnetic field that depolarizes neurons. • Outpatient procedure • Safe and well tolerated • Efficacy =?

  13. On the Horizon • Starting 2 versus 1agent at treatment initiation • NMDA receptor antagonists (ketamine) • Corticotropin releasing factor-1 (CRF1) antagonists • Glucocorticoid receptor antagonists • Substance P receptor antagonists • Melanocyte inhibiting factor (nemifitide) • Melatonin receptor antagonists • Focal and deep brain stimulation therapies

  14. Case B - Nicole Nicole is a 21 y/o junior who presents complaining of panic attacks and anxiety. In talking with her, she states that she feels no one likes her and she is just a failure. She worries about her family and her dying grandmother. Her sleep is poor and she has lost interest in food. She isn’t interested in her school work and wonders if she would just be better off dead.

  15. Differential Diagnosis of “Anxiety” • Secondary to a medical condition • Substance induced • Major depression • Mania/hypomania • Psychotic disorder • Personality disorder • Anxiety disorder Anxiety is a non-specific symptom; Need to determine the cause

  16. DSM-IV vs. DSM-5 DSM-!V DSM-5 Anxiety Disorders Specific phobia Social anxiety disorder Panic disorder Generalized anxiety disorder O-C & Related Disorders OCD Trauma & Stressor Related Disorders PTSD Acute stress disorder Adjustment disorder • Anxiety Disorders • Specific phobia • Panic disorder • Social phobia • OCD • PTSD • Acute stress • Generalized anxiety disorder • Adjustment disorders

  17. Pharmacologic Treatments • Benzodiazepines • SSRI/SNRI • Tricyclic antidepressants • Other agents

  18. J of Clin. Psychiatry, 60(5), 252, May 1999

  19. SSRI/SNRIs in Anxiety Disorders Advantages • High efficacy • Non-addicting • Effective for a number of conditions Disadvantages • Can take 2-8 weeks or longer to be effective • Side effects • Drug interactions • Discontinuation syndrome

  20. Other Options for Anxiety Disorders • Buspirone • Beta blockers (e.g. propranolol) • Tricyclic antidepressants • Vilazodone (SSRI/5-HT1A Partial agonist) • Antipsychotics • Typical (e.g. Trifluoperazine) • Atypical (e.g. Quetiapine) • Antihistamines • Hydroxyzine • Anticonvulsants • Gabapentin/Pregabalin • Combinations

  21. Psychotropic Choice for Specific Conditions

  22. Case C - Marc Marc is a 22 y/o junior who presents requesting a refill of his medication. He tells you he was diagnosed with bipolar disorder and ADHD and is currently prescribed: lamotrigine 200 mg daily, escitalopram 10 mg daily, clonazepam 1 mg BID, zolpidem 5 mg HS, and Adderall-XR 20 mg qAM.

  23. Bipolar disorder vs. Bipolar spectrum disorder • Definition – Spectrum disorder • Epidemiology (lifetime prevalence) • Bipolar I disorder = 1% • Bipolar spectrum disorders = 2.6 – 6.5% • Delayed diagnosis/missed diagnosis • Screen depressed patients for possible bipolar depression (e.g. MDQ, BSRS)

  24. Mood Disorders – A Spectrum Disease

  25. The Heterogeneity of Bipolar Disorder Taken from: http://www.psychosis-bipolar.com/information-about-psychoses-57.htmlTaken

  26. Lifetime Comorbidity with Bipolar Disorder

  27. Treating Bipolar Disorder • Use mood charting. • Combination pharmacotherapy is the rule rather than the exception. • Mood stabilizers are the cornerstone of therapy. • Optimize therapeutic effect and tolerability while minimizing side effects. • Antidepressants may worsen the disease course.

  28. Pharmacotherapy for Mood Disorders 1. Mood stabilizers Lithium 2. Anticonvulsant Mood Stabilizers Valproic acid (Depakote) Carbamazepine (Tegretol) Lamotrigine (Lamictal) 3. Atypical Antipsychotics See Chart 4. Combination Olanzapine/fluoxetine (Symbyax)

  29. FDA Approved Indications for Atypical Antipsychotics OLA = Olanzapine, RIS = Risperidone, ILO = Iloperidone, QUE = Quetiapine, ZIP = Ziprasidone, ARI = Aripiprazole, ASEN = Asenapine, LUR lurasidone

  30. Pharmacotherapy for Bipolar Disorder

  31. Questions?

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