Pharmacological Treatment of PTSD

1. Pharmacological Treatment of PTSD Margarita Tartakovsky March 22, 2006

2. Overview DSM criteria for PTSD Treatment Treatment of choice Issues with pharmacological treatment Limitations of research studies Medications Implications for clinical practice

3. DSM Criteria A. Exposed to a traumatic event: experience, witness, or confronted with event(s) with actual/threatened death/ serious injury AND response involved intense fear, helplessness, or horror B. Event persistently re-experienced: recurrent and intrusive distressing recollections/dreams acting or feeling as if the traumatic event were recurring Intense psychological distress at exposure to things reminiscent of event physiological reactivity

4. DSM Criteria C. Persistent avoidance associated with trauma: efforts to avoid thoughts, feelings avoidance of people, places associated with trauma recall inability diminished interest detachment feelings restricted range of emotions negative outlook toward future

5. DSM Criteria D.� Persistent symptoms of increased arousal: 2 or more of the following difficulty falling or staying asleep irritability or outbursts of anger difficulty concentrating hypervigilance exaggerated startle response

6. DSM Criteria E.�Duration of symptoms is more than 1 month F.�Causes clinically significant distress and/or impairment in social, occupational, and/or other important areas of functioning Acute: less than 3 months Chronic: �more than 3 months Delayed Onset: �onset of symptoms is at least 6 months after the incident

7. Symptom Clusters Re-experiencing: intrusive recollections, recurrent dreams, dissociative flashbacks Avoidance and numbness: avoidance of cognitions/activities related to trauma, decreased interest, feeling detached Hyperarousal: hypervigilance, insomnia, exaggerated startle response

8. Systems involved in PTSD Neurotransmitter sensitization ? release of noradrenaline and ? autonomic activity Dopamine Amygdala and the hippocampus Amygdala � involved in fear conditioning and extinction Hippocampus � plays important role in memory; involved in mediating traumatic memories and learned responses to cues PET studies = veterans show ? right amygdala activity when exposed to combat movies MRI studies = male combat veterans + female survivors of childhood sexual abuse have shrunken hippocampal volumes

9. More on systems Excessive cortisol and glutamate activity Human + animal studies = immediately after severe trauma, ? in cortisol and glutamate can reach toxic levels + damage parts of brain (affect regulation) Serotonin Preclinical studies = serotonergic pathways project to areas crucial in fear responses Clinical studies = serotonin agonist, mCPP provokes PTSD sxs Important to note: kindling effect � repeated traumatic episodes change brain functioning and brain morphology

10. Treatment Psychotherapy is the treatment of choice Meds are not the primary treatment but should target specific symptoms as they arise Restoring a sense of control over emotions

11. Issues with pharmacological treatment Efficacy across symptom clusters Comorbidity/Associated sxs depression and substance abuse common guilt, shame, distrust significant marital, occupational, financial, health problems Discontinuation of meds ? original symptoms returning Response to meds not guaranteed Changes not necessarily large

12. Methodological issues in research studies (1) Placebo effect (2) Small samples (3) SSRIs studies with mostly female participants (4) Exclusion of patients with comorbid substance abuse

13. Meds Tricyclic Antidepressants (TCAs) Benzodiazepines Antipsychotics Selective Serotonin Reuptake Inhibitors

14. TCAs 1st antidepressants used Prevent reuptake of monoamines (serotonin or norepinephrine) by the presynaptic neurons in the CNS, thus prolonging the effects of these NTs Numerous side effects: blurred vision, dry mouth, constipation, weight gain, dizziness when changing position, increased sweating, difficulty urinating, changes in sexual desire, decrease in sexual ability, muscle twitches, fatigue and weakness Overdose ? delirium, hypotension, cardiac arrhythmias and death.

15. Benzodiazepines Relatively fast-acting Use has declined concerns over dependence and abuse Lower anxiety by ?vigilance, eliminating muscle tension, and causing sedation act on the g-aminobutyric acid (GABA)/benzodiazepine (BZ) receptor complex Side effects: concentration problems, a mild form of amnesia, drowsiness and a loss of coordination; fatigue and mental slowing or confusion dangerous to drive or operate heavy machinery

16. Antipsychotics Traditional antipsychotic meds rarely considered for use unless psychotic symptoms present Atypical antipsychotics used to treat some core symptoms Helpful with severe treatment resistant PTSD

17. SSRIs 1st line of treatment Antidepressants that block reuptake of serotonin at presynaptic neurons in the brain Side effects: nausea, sweating, fatigue, sleepiness, and sexual side effects. Generally safer than TCAs if overdose is taken

18. SSRIs available in U.S. Generic Name Brand Name citalopram Celexa / Cipramil fluoxetine Prozac fluvoxamine Luvox paroxetine Paxil / Seroxat sertraline Zoloft / Lustral Note: Right now sertraline and paroxetine have FDA approval for treating PTSD http://www.twilightbridge.com/psychiatryproper/ailmentguide/ptsd/medication.htm

19. Going to Meds for treatment Psychotherapy or exposure-based treatment intolerant Low level of cognitive functioning When sxs become too intense or interfere with daily life, short-term meds: Intrusive experiences, flashbacks Transient psychosis Marked derealization Avoidance/numbing Longer term meds: major depression, panic disorder, persistent psychotic sxs

20. Considerations for clinical practice No empirical data for prescribing decisions Clinical judgment important!

21. Resources Cooper, J., Carty, J., & Creamer, M. (2005). Pharmacotherapy for posttraumatic stress disorder: Empirical review and clinical recommendations. Australian and New Zealand Journal of Psychiatry, 39, 674-682. Preston, J.D., O�Neal, J. H., & Talaga, M.C. (2005). Post-Traumatic Stress Disorder. Handbook of clinical psychopharmacology for therapists. Harbinger Publications, 129-136. Ratna, L., & Barbenel, D. (1997). The pharmacotherapy of post traumatic stress disorder. A literature review and case report of treatment with nefazodone. International Journal of Psychiatry in Clinical Practice, 1, 169-177. http://www.ncptsd.va.gov/facts/disasters/fs_medication_disaster.html http://www.nimh.nih.gov/publicat/reliving.cfm http://ptsd.factsforhealth.org/medfaq.html