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  • The Carlat Psychiatry Report
  • Problems with Generics (May)
  • A Review of Medications for PTSD, With a Focus on Topiramate

A Review of Medications for PTSD, With a Focus on Topiramate

The Carlat Psychiatry Report, Volume 19, Number 5, May 2021
https://www.thecarlatreport.com/newsletter-issue/tcprv19n5/

From The Carlat Psychiatry Report, May 2021, Problems with Generics

Issue Links: Learning Objectives | Editorial Information | PDF of Issue

Topics: PTSD

Print Friendly, PDF & Email

Paul Riordan, MD.

Assistant Consulting Professor of Psychiatry, Duke University.

Dr. Riordan has disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

A new patient comes into your office for an assessment. He tells you he cannot keep living this way. He shops at Walmart at 3 am to avoid strangers. He startles easily and suffers from nightmares and flashbacks related to a trauma he experienced in the Army. He’s tried sertraline and venlafaxine for PTSD but did not find them helpful and wants to try something else. You offer a referral for trauma-focused therapy, but he refuses, saying “I don’t want to talk to anyone.”

Are there any other medications that could help? When it comes to PTSD, trauma-focused therapy is first-line. It is backed by solid data with a large effect size, while medications have only mild treatment effects (Lee DJ et al, Depress Anxiety 2016;33(9):792–806). A possible exception to this rule is that patients who choose their preferred treatment do better when they receive their choice—meaning patients who prefer pills do better when they get pills (Mergl R et al, Psychother Psychosom 2011;80(1):39–47).

Which medications work in PTSD?
Sertraline and paroxetine have FDA approval in PTSD, but there is nothing about the pathophysiology of PTSD that points to SSRIs as the cure. In some countries, SSRIs did not gain approval because they mainly worked in civilian trauma and not military trauma, but military trauma is more difficult to treat whether with medications or therapy. A new meta-analysis—the largest to date—compared effect sizes of 26 medications across 58 studies that had a total of nearly 7,000 patients with PTSD (de Moraes Costa G et al, J Psychiatr Res 2020;130:412–420).

What did the study find? Only seven medications—fluoxetine, paroxetine, quetiapine, risperidone, sertraline, topiramate, and venlafaxine—were better than placebo. Missing from this list is prazosin; it no longer passes statistical muster due to a large negative trial of 304 veterans with PTSD (Raskind MA et al, N Engl J Med 2018;378(6):507–517), but there were flaws with that study that lead some to believe prazosin does work in a subset of patients (see TCPR, April 2019).

Table: Seven Medications for PTSD

Table: Seven Medications for PTSD

(Click to view full-size PDF.)

As expected, the SSRIs and SNRIs had small benefits, with effect sizes ranging from 0.2 to 0.35—about the same as the small effect sizes observed for antidepressants in depression (Ormel J et al, Psychol Med 2019;50(2):177–186). Fluoxetine had the best balance of efficacy and acceptability, but that was mainly due to high tolerability, since its benefit was small. Despite the small effect sizes, our confidence in those benefits is high, with each medication having 650–1,400 total participants across their trials.

In contrast, the effect sizes were larger (0.5–0.6) for a few off-label medications: topiramate, risperidone, and quetiapine. However, there were only a few studies backing these medications, with only 70–100 patients each—so while they show promise, it’s not definite since small studies are notorious for inflated effect sizes.

Benefits of topiramate for PTSD
Most surprisingly, topiramate came out on top as having the greatest benefit for PTSD, with a medium effect size (0.57). There is a lot of uncertainty around that figure, as it was based on only two randomized trials involving 73 civilian patients. However, three randomized trials of 137 veterans were excluded because they focused on treatment-resistant PTSD (two studies) or on comorbid alcohol use disorder with PTSD symptoms as a secondary outcome (one study). If these studies are included, the total n becomes 210, with one positive trial, three trials trending toward significance, and one negative trial. The negative trial, which focused on treatment-resistant PTSD in veterans, had a high dropout rate due to side effects (Lindley SE et al, J Clin Psychopharmacol 2007;27(6):677–681). In the other trials, while topiramate caused side effects like dizziness, paresthesias, and memory problems, it did not lead to more dropouts.

What did topiramate help with? Across studies, it appeared most helpful for the “reexperiencing” symptoms—flashbacks, intrusive memories, and nightmares, with less benefit for avoidance and numbing symptoms.

Topiramate demonstrated other benefits relevant to PTSD. For example, in one trial, veterans with PTSD who took topiramate had 55% fewer standard drinks per week than those taking placebo (Batki SL et al, Alcohol Clin Exp Res 2014;38(8):2169–2177). Topiramate is also FDA approved for migraine prophylaxis and—based on small controlled trials—may help with obesity, borderline personality disorder, cocaine abuse, and impulse control disorders (Nourredine M et al, CNS Drugs 2021;35(2):177–213; Varghese BS et al, Indian J Pharmacol 2010;42(3):135–141). Unlike the antidepressants, it is safe in bipolar disorder.

How to use
Slow titration is recommended for topiramate’s FDA-approved indications (migraines and epilepsy), and we have found that strategy helpful in reducing side effects like dizziness and cognitive impairment. For PTSD, start at 25 mg nightly and raise by no more than 25 mg/week toward a target dose of 100–300 mg daily. With a 21-hour half-life, nightly dosing is acceptable, but opt for divided dosing if the patient experiences side effects as the level peaks.

The most common side effects to watch for are dizziness, paresthesias, somnolence, and cognitive impairment. For cognition, topiramate typically affects word finding and verbal fluency—tested by listing as many animals as possible in 60 seconds (Thompson PJ et al, J Neurol Neurosurg Psychiatry 2000;69(5):636–641). Rare side effects to watch for include kidney stones, glaucoma, increased body temperature, and metabolic acidosis.

TCPR Verdict: Topiramate has potential as second- or third-line pharmacology for PTSD after a trial of SSRIs/SNRIs, and it may be closer to first-line for patients with comorbid alcohol use disorder.

podcastsRelated Podcast Episode:
13 Ways to Use Topiramate
We ask the big questions: Is topiramate a drug or a sugar? Do you need to use the FDA-approved combo pill for weight loss? And which of its 13 off-label psychiatric uses are ready for clinical practice?

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  • The Difficult Patient (January)

2021

  • Bipolar Disorder (November/December)
  • Mood Disorders (October)
  • Overdiagnosis (September)
  • Therapy (August)
  • Depression (June/July)
  • Problems with Generics (May)
  • Metabolism and Mental Health (April)
  • Stopping Psych Meds Part 2 (March)
  • Stopping Psych Meds Part 1 (February)
  • Mind-Gut Connection (January)

2020

  • Esketamine (January)
  • Telepsychiatry (May)
  • Mind-Gut Connection (January)
  • Practical Psychotherapy (November/December)
  • Mood and Menopause (October)
  • When to Use Lithium (September)
  • Traumatic Brain Injury (August)
  • Borderline Personality Disorder (June/July)
  • Psychopharmacology Algorithms (April)
  • Bipolar II (March)
  • Inflammation and Depression (February)

2020

  • Mood Disorders in Children and Adolescents (Oct/Nov/Dec)
  • Identity & Culture in Children and Adolescents (July/August/September)
  • Psychosis in Children and Adolescents (April/May/June)
  • ADHD in Children and Adolescents (Jan/Feb/Mar)

2020

  • Harm Reduction (January/February)
  • Substance Use in Health Professionals (March/April)
  • Alternative Treatment in Addiction (November/December)
  • Social Aspects of Addiction (September/October)
  • Opioid Use Disorder Treatment (July/August)
  • Emerging Risks for Old Medications (May/June)

2019

  • Depression (May)
  • Adult ADHD (November/December)
  • Mental Health Apps (October)
  • How to Talk about Medication (September)
  • Side Effects Part II (August)
  • Side Effects Part I (June/July)
  • Sleep (April)
  • Parenting, Pregnancy, and Prevention (March)
  • Dark and Light Therapy (February)
  • Deprescribing (January)

2018

  • Drug Metabolism (November/December)
  • Working With Transgender Patients (October)
  • Emergency Psychiatry (September)
  • Treatment-Resistant Depression (July/August)
  • Neurobiology (June)
  • Anxiety (May)
  • Neurofeedback (April)
  • Antipsychotics Update (March)
  • Working With Families (February)
  • Bipolar Disorder (January)

2017

  • PTSD (December)
  • Retirement (November)
  • Intellectual Disability (September/October)
  • Antidepressants (July/August)
  • Personality Disorders (June)
  • Dementia (May)
  • Cognitive Behavior Therapy Techniques (April)
  • Pharmacogenetics (March)
  • Treating Psychosis (February)
  • Adult ADHD (January)

2016

  • Complementary and Alternative Medicine in Psychiatry (November/December)
  • Side Effects (October)
  • Pain Management (September)
  • Medication in Pregnancy (July/August)
  • Psychoanalysis in Modern Psychiatry (June)
  • Correctional Psychiatry (May)
  • Antidepressant Roundup (April)
  • Burnout (March)
  • Private Practice (February)
  • Bipolar Disorder (January)

2015

  • Psychiatry and General Medicine (November/December)
  • Biomarkers in Psychiatry (May)
  • Telepsychiatry (October)
  • Sleep Disorders (September)
  • Interventional Psychiatry (July/August)
  • Eating Disorders (June)
  • Psychotherapy Updates (April)
  • Topics in Geriatric Psychiatry (March)
  • Antipsychotics Update (February)
  • Risk Management (January)

2014

  • Bipolar Disorder (November/December)
  • Pharmacogenetics (October)
  • Keeping up in Psychiatry (September)
  • Research in Psychiatry (July/August)
  • Marijuana (June)
  • Psychiatric Diagnosis (May)
  • Issues in Psychopharmacology (April)
  • Schizophrenia (March)
  • Women’s Psychiatry (February)
  • Ethics in Psychiatry (January)

2013

  • Military Psychiatry (December)
  • Depression (November)
  • Treatment of Dementia (October)
  • Anxiety Disorders (September)
  • Natural and Alternative Treatments in Psychiatry (July/August)
  • Autism Spectrum Disorder (June)
  • Practice Tips (May)
  • Substance Abuse (April)
  • Medicolegal Topics (March)
  • End of Life Care (February)
  • Antipsychotic Update (January)

2012

  • Screening Tools and Tips (December)
  • Medical Comorbidities (November)
  • Devices in Psychiatry (October)
  • Eating Disorders (September)
  • Bipolar Disorder (July/August)
  • Risk Management (June)
  • Antidepressant Roundup 2012 (May)
  • Gender and Sexuality (April)
  • Personality Disorders (March)
  • ADHD (February)
  • Natural Treatments in Psychiatry (January)

2011

  • Electronic Medical Records (December)
  • Insomnia (November)
  • Psychotherapy (October)
  • Alcoholism (September)
  • Anxiety Disorders (July/August)
  • Schizophrenia (June)
  • Managing Side Effects (May)
  • Antidepressant Roundup 2011 (April)
  • DSM-5 and Diagnostic Issues (March)
  • Drug-Drug Interactions (February)
  • Bipolar Disorder (January)

2010

  • Hospital Psychiatry (December)
  • Psychiatric Medication in Pregnancy (November)
  • Maintenance of Certification (October)
  • The Neuroscience of Psychotherapy (September)
  • Treatment of Depression (July/August)
  • Email and the Internet in Psychiatry (June)
  • Substance Abuse (May)
  • The Diagnosis and Treatment of Dementia (April)
  • Ethics in Psychiatry (March)
  • Natural Treatments in Psychiatry (February)
  • ADHD (January)

2009

  • Treating Schizophrenia (December)
  • Treatment for Anxiety Disorders (November)
  • The Latest on Antidepressants (October)
  • Topics in Neuropsychiatry (September)
  • The Interface of Medicine and Psychiatry (July/August)
  • Generic Medications in Psychiatry (June)
  • The Treatment of Eating Disorders (May)
  • Healthcare Policy and Psychiatry (April)
  • Antipsychotic Roundup 2009 (March)
  • Psychiatric Medication in Pregnancy and Lactation (February)
  • Transcranial Magnetic Stimulation (January)

2008

  • Treating Fibromyalgia and Pain in Psychiatry (December)
  • Issues in Child Psychiatry (November)
  • Improving Psychiatric Practice (October)
  • Treating Personality Disorders (September)
  • Bipolar Disorder (July/August)
  • Antipsychotic Roundup 2008 (June)
  • Atypical Antipsychotics in Clinical Practice (February)
  • Neuropsychological Testing (May)
  • Psychiatric Medications: Effects and Side Effects (April)
  • Update on Substance Abuse (March)
  • Anticonvulsants in Psychiatry (February)
  • Brain Devices in Psychiatry (January)

2007

  • The Treatment of Insomnia (December)
  • Avoiding Malpractice in Psychiatry (November)
  • Update on Eating Disorders (October)
  • Complex Psychopharmacology (September)
  • Laboratory Testing in Psychiatry (August)
  • Psychotherapy in Psychiatry (July)
  • Posttraumatic Stress Disorder (June)
  • Topics in Geriatric Psychiatry 2007 (May)
  • Pregnancy and Menopause in Psychiatry (Apil)
  • Antipsychotic Roundup 2007 (March)
  • Understanding Psychiatric Research (February)
  • Antidepressant Round-up 2007 (January)

2006

  • Technology and Psychiatric Practice (December)
  • The Use of MAOIs (November)
  • Medication Treatment of Depression (January)
  • Seasonal Affective Disorder (October)
  • Treatment of ADHD (September)
  • Topics in Bipolar Disorder (August)
  • Neurotransmitters in Psychiatry (July)
  • Treating Substance Abuse (June)
  • The STAR*D Antidepressant Trial (May)
  • Natural Treatments in Psychiatry (April)
  • Medication Treatment of Anxiety (March)
  • Panic Disorder: Making Treatment Work (March)
  • Antipsychotic Roundup 2006 (February)
  • Antidepressant Roundup 2006 (January)

2005

  • Self-Help Books and Psychiatry (December)
  • Genetics and Psychiatry (November)
  • Pregnancy and Psychiatric Treatment (October)
  • Benzodiazepines and Hypnotics in Psychiatry (September)
  • Geriatric Psychiatry Update (August)
  • Chart Documentation in Psychiatry (July)
  • The Treatment of Bipolar Disorder (June)
  • Weight Loss and Smoking Cessation in Psychiatry (May)
  • Treating ADHD (April)
  • Drug Industry Influence in Psychiatry (March)
  • Atypical Antipsychotics 2005 (February)
  • Antidepressant Roundup 2005 (January)

2004

  • Sexual Dysfunction (December)
  • Suicide Prevention (November)
  • To Sleep, To Awake (October)
  • Women’s Issues in Psychiatry (September)
  • OCD: An Update (August)
  • Chronic Pain and Psychiatry (July)
  • Neuroimaging in Psychiatry (June)
  • Natural Medications in Psychiatry (May)
  • Posttraumatic Stress Disorder (April)
  • Treatment of Alcoholism (March)
  • Battle of the Atypicals (February)
  • Antidepressant Roundup, 2004 (January)

2003

  • Research Methods in Psychiatry (December)
  • Antidepressants in Children (November)
  • The Treatment of Dementia (October)
  • Bipolar Disorder, Part II: The Novel Anticonvulsants (September)
  • Bipolar Disorder: The Basics (August)
  • Drug-Drug Interactions in Psychiatry (July)
  • Managing Antidepressant Side Effects (June)
  • Antidepressants in Pregnancy and Lactation (May)
  • ADHD: Medication Options (April)
  • Panic Disorder: Making Treatment Work (March)
  • Atypical Antipsychotics in Clinical Practice (February)
  • Medication Treatment of Depression (January)

2019

  • Autism in Children and Adolescents (November/December)
  • Depression in Children and Adolescents (May/June/July/August)
  • Substance Use in Children and Adolescents (September/October)
  • Trauma in Children and Adolescents (March/April)
  • Anxiety in Children and Adolescents (January/February)

2018

  • Psychotropic Risks in Children and Adolescents (May/June)
  • ADHD in Children and Adolescents (November/December)
  • Depression in Children and Adolescents (September/October)
  • Autism in Children and Adolescents (July/August)
  • Anxiety in Children and Adolescents (March/April)
  • Suicide in Children and Adolescents (January/February)

2017

  • Adolescents (November/December)
  • ADHD in Children and Adolescents (September/October)
  • Psychosis in Children and Adolescents (August)
  • PANDAS, PANS, and Related Disorders (June/July)
  • Marijuana in Children and Adolescents (May)
  • Tourette’s and Other Tic Disorders in Children and Adolescents (March/April)
  • Autism in Children and Adolescents (January/February)

2016

  • Gender Dysphoria in Children and Adolescents (November/December)
  • Technology Issues With Children and Adolescents (September/October)
  • Mood Dysregulation in Children and Adolescents (July/August)
  • Eating Disorders in Children and Adolescents (May/June)
  • Conduct Disorder in Children and Adolescents (April)
  • Sleep Disorders in Children and Adolescents (March)
  • ADHD in Children and Adolescents (January/February)

2015

  • Antidepressant Use in Children (November/December)
  • Foster Care and Child Psychiatry (September/October)
  • Autism (July/August)
  • Trauma (May/June)
  • Anxiety Disorders (April)
  • Schools and Psychiatry (March)
  • Emergency Psychiatry in Children (January/February)

2014

  • Antipsychotics in Children (December)
  • ADHD (November)
  • Gender and Sexuality (September/October)
  • Psychotic Symptoms (Summer)
  • Medication Side Effects (May)
  • Food and Mood (April)
  • Learning and Developmental Disabilities (February)

2013

  • Complex Practice Issues (December)
  • Diet and Nutrition (November)
  • Child Psychiatry in DSM-5 (August/September)
  • Medication Side Effects and Interactions (June/July)
  • Problematic Technology (March/April)
  • Autism Spectrum Disorders (January/February)

2012

  • Bipolar Disorder (December)
  • Substance Abuse (October/November)
  • Transitional Age Youth (July/August)
  • Rating Scales (May/June)
  • Eating Disorders (March/April)
  • Behavioral Disorders (February)

2011

  • Treatment of Anxiety Disorders (December)
  • Trauma (November)
  • Bullying and School Issues (October)
  • Hidden Medical Disorders (August)
  • OCD and Tic Disorders (June)
  • Suicide and Non-Suicidal Self Injury (April)
  • Sleep Disorders (March)
  • ADHD (January)

2010

  • Use of Antipsychotics in Children and Adolescents (December)
  • Learning and Developmental Disabilities (October)
  • Major Depression (September)
  • Treating Children and Families (July)
  • The Explosive Child (May)

2019

  • Dual Diagnosis in Addiction Medicine (May/June)
  • Medical Issues in Addiction Practice (November/December)
  • Alcohol Addiction (September/October)
  • Legal Issues in Addiction Medicine (July/August)
  • Traumatic Brain Injury and Addiction (March/April)
  • Board Certification in Addiction Medicine (January/February)

2018

  • Opioid Addiction (November/December)
  • Addiction in Older Adults (October)
  • Sleep Disorders and Addiction (September)
  • Adolescent Addiction (July/August)
  • Pain and Addiction (May/June)
  • Cannabis and Addiction (March/April)
  • Stigma and Addiction (January/February)

2017

  • Pregnancy and Addiction (November/December)
  • Detox (Sepember/October)
  • Dual Diagnosis (August)
  • Alternatives to 12-Step Programs (June/July)
  • Recovery (May)
  • Psychiatric Uses of Street Drugs (March/April)
  • Sex Addiction (January/February)

2016

  • Prescription Drug Monitoring Programs (PDMPs) (November/December)
  • Addiction in Health Care Professionals (September/October)
  • Dialectical Behavior Therapy in Addiction (August)
  • Motivational Interviewing (June/July)
  • Benzodiazepines (May)
  • Opioid Addiction (March/April)
  • Families and Substance Abuse (January/February)

2015

  • The Twelve Steps (November/December)
  • Designer Drugs (September/October)
  • Residential Treatment Programs Decoded (July/August)
  • Nicotine and E-Cigarettes (June)
  • Drug Screening (April/May)
  • Integrating Therapy and Medications for Alcoholism (March)
  • Detoxification Protocols (January/February)

2014

  • Behavioral Addictions (December)
  • Risk and Reimbursement (November)
  • Stimulant Abuse (September/October)
  • Self-Help Programs (June)
  • Opioid Addiction (May)
  • Coping with Bad Outcomes (March)
  • Change Management in Addiction Treatment (January/February)

2013

  • Cocaine Addiction (December)
  • Relapse Prevention (November)
  • Cannabis Addiction (August/September)
  • Addiction in DSM-5 (June/July)
Editor-in-Chief

Chris Aiken, MD

Dr. Aiken is the director of the Mood Treatment Center in North Carolina, where he maintains a private practice combining medication and therapy along with evidence-based complementary and alternative treatments. He has worked as a research assistant at the NIMH and a sub-investigator on clinical trials, and conducts research on a shoestring budget out of his private practice.

Full Editorial Information

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