It is usually late when people read about this.
You have done everything you could. Three medications. A course of therapy finished, another one stopped. The sleep is still bad. Around eleven at night you find an article about ketamine for PTSD and think: why has nobody offered me this?
Fair question. The 2023 VA/DoD clinical practice guideline suggests against ketamine for PTSD, and its use for any psychiatric condition is off-label and considered investigational by the FDA. Narrow situations remain where it is worth discussing, most often when treatment-resistant depression is the more disabling problem.
We offer ketamine infusions here in Fort Worth.
In crisis or thinking about harming yourself? Call or text 988 for the Suicide & Crisis Lifeline, 24/7. For scheduling, call 817-659-7344. We are an outpatient practice, not a crisis service.
What the 2023 VA/DoD guideline says about ketamine for PTSD
The VA and Department of Defense publish a joint clinical practice guideline for PTSD. Version 4.0, from June 2023, is the most careful public map of this evidence. Recommendation 18 reads, in full:
“We suggest against divalproex, guanfacine, ketamine, prazosin, risperidone, tiagabine, or vortioxetine for the treatment of PTSD. (Weak against | Reviewed, New-replaced)”
Two things matter. First, it is genuinely against. In the guideline’s own vocabulary, “Weak against” corresponds to “We suggest against . . .”, while “Strong against” means “We recommend against . . .” Benzodiazepines and cannabis sit in that stronger category. Ketamine does not.
Consider what a weak rating is built from. The Work Group’s “confidence in the quality of the evidence was very low,” and under this guideline’s method “the determination of the strength of the recommendation is more directly linked to the confidence in the quality of the evidence. The same discussion concludes that “the benefits of treating PTSD using divalproex, guanfacine, ketamine, prazosin, risperidone, tiagabine, or vortioxetine as monotherapy were outweighed by the potential harm.” Weak does not mean ignorable: the guideline is explicit that “a recommendation’s strength (i.e., Strong versus Weak) is distinct from its clinical importance (e.g., a Weak recommendation is evidence based and still important to clinical care).” And nowhere does it recommend ketamine for PTSD in any combination.
Is ketamine FDA approved for PTSD?
No.
Ketamine is an old anesthetic. Its labeling covers use as a sole anesthetic agent, for induction, and as a supplement to other anesthetics. No psychiatric indication appears in it: not depression, not PTSD. Every psychiatric use of IV ketamine, including ours, is off-label, and the FDA considers it investigational. Our ketamine infusion therapy page says so. Spravato, intranasal esketamine, is a separate approved product we do not offer.
What the randomized trials actually found
This is a small literature: six randomized trials, 221 people between them, only one larger than a few dozen.
| Trial | Design | Participants | Result |
| Feder 2014, JAMA Psychiatry | 1 infusion, crossover vs midazolam | 41 recruited | PTSD severity lower at 24 hours; proof-of-concept |
| Feder 2021, Am J Psychiatry | 6 infusions over 2 weeks vs midazolam | 30 | 67% vs 20% response; median loss of response 27.5 days after the course |
| Abdallah 2022, Neuropsychopharmacology | 8 infusions, 2 doses vs placebo | 158 veterans and service members | No effect on either PTSD measure; depression improved on a secondary measure |
The 2014 crossover trial was the encouraging one, and its authors hedged: “proof-of-concept,” and “if replicated, these findings may lead to novel approaches” to treating the condition. The 2021 follow-up’s 67 percent response rate sounds decisive until you notice that thirty people in two arms is fifteen apiece.
The trial that failed, and why it matters most
In 2022, a multi-site team published a trial of 158 veterans and service members whose PTSD had not responded to antidepressants, randomized to placebo, low-dose or standard-dose ketamine.
The authors: “There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5.” Their conclusion: “This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms.”
One secondary finding did separate from placebo: “The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo.” The MADRS was a secondary outcome; the primary was the PCL-5, and the authors stayed modest: “secondary analyses suggested that the standard dose exerted rapid antidepressant effects.” A secondary signal in a trial that missed its primary endpoint is a reason to keep looking, not a plan. Hold onto it anyway.
The guideline cites this trial when it says “the Weak against recommendation on ketamine was maintained, reflecting findings of recently published clinical trials.” Its crosswalk of the 2017 edition lists ketamine inside a Strong against recommendation, so if the rating moved, it moved toward the middle.
What happens when you pool everything
A 2024 systematic review in the European Journal of Psychotraumatology pooled every randomized trial it could find: six studies, 221 participants. It found “a small advantage for ketamine over control conditions” (g = 0.27), but corrected for publication bias that fell to g = 0.20, crossing zero; at two weeks, g = 0.17, also crossing zero. A post-hoc look at 24 hours after the first infusion put ketamine ahead of passive controls like saline (g = 0.44) but not active controls (g = 0.24, crossing zero). The authors concluded that “placebo is the likely mechanism behind reported therapeutic effects.”
The VA’s patient page on medications for PTSD lists three: sertraline, paroxetine, and venlafaxine. Ketamine is not on it.
What comes first
The guideline is plain about sequence. Recommendation 7 is Strong for “individual psychotherapies, listed in Recommendation 8, over pharmacologic interventions for the treatment of PTSD.” Recommendation 8 names “Cognitive Processing Therapy, Eye Movement Desensitization and Reprocessing, or Prolonged Exposure” as the “individual, manualized trauma-focused psychotherapies,” also Strong for. Then Recommendation 15 is Strong for paroxetine, sertraline, or venlafaxine.
PRISM, which we offer, belongs to a later group. It is a GrayMatters Health device, FDA-cleared as “an adjunctive treatment of symptoms associated with posttraumatic stress disorder (PTSD), to be used under the direction of a healthcare professional, together with other pharmacological and/or non-pharmacological interventions.” Cleared, not approved; adjunctive, meaning alongside rather than instead of. The same guideline judges the underlying technology: Recommendation 24 finds “insufficient evidence to recommend for or against” neurofeedback for PTSD, grouping it with rTMS and other somatic therapies as Neither for nor against. Clearance means substantial equivalence to earlier biofeedback devices, not endorsement. A course here runs about 15 sessions.
Getting the diagnosis right comes first. Broken sleep, irritability, and restless drive can read as PTSD arousal or as hypomania, which changes what is safe to prescribe. Sertraline’s labeling warns that “in patients with bipolar disorder, treating a depressive episode with ZOLOFT or another antidepressant may precipitate a mixed/manic episode,” and tells prescribers to screen for that history.
Where a conversation about ketamine can still be reasonable
Only once that sequence has had a genuine try does a conversation about anything else sensibly begin. One such conversation exists, and it is not about PTSD.
The same two agencies publish a separate guideline for major depressive disorder. Its 2022 Recommendation 19 reads: “For patients with MDD who have not responded to several adequate pharmacologic trials, we suggest ketamine or esketamine as an option for augmentation.” The label is Weak for, and that guideline is explicit that ketamine “is not recommended as initial treatment.”
So the same institution suggests against ketamine for PTSD and suggests for it, cautiously, in depression several medications have not touched. Both can be true; they answer different questions. Recall the 2022 trial: PTSD scores did not move, depression scores did. In someone carrying both, an infusion series may do something for the depression while leaving PTSD symptoms roughly where they were. That use is off-label and considered investigational by the FDA too, and no one can promise a response.
That is not a PTSD protocol. Our ketamine page is written around severe treatment-resistant depression and related mood disorders, deliberately. Our PTSD service page does say Dr. Ghelber “may recommend ketamine infusion therapy” when symptoms persist despite repeated attempts; what that means is this conversation, aimed at a co-occurring depression, not a PTSD indication. Visits are self-pay, with rates on our Price List.
If you are in North Texas and have never had a full course of trauma-focused therapy, ask about that first. No psychiatric medication should be stopped abruptly, and PTSD decisions belong with a prescriber who knows your history.
Frequently asked questions
Does the VA recommend against ketamine for PTSD?
The 2023 VA/DoD guideline suggests against it. In its vocabulary “Weak against” means “We suggest against,” while “Strong against,” used for benzodiazepines and cannabis, means “We recommend against.” So it is a suggestion, not a prohibition, tied to very low confidence in the evidence. The Work Group still concluded that potential harm outweighed the benefits.
Is ketamine FDA approved to treat PTSD?
No. Ketamine’s labeling covers anesthesia only, with no psychiatric indication of any kind, so use for depression or PTSD is off-label and considered investigational by the FDA. Spravato, intranasal esketamine, is a separate approved product for treatment-resistant depression, not PTSD, and is not offered here. We offer IV racemic ketamine.
How many people have actually been studied?
Fewer than most people expect. A 2024 meta-analysis pooled six randomized trials totaling 221 participants, and the largest, in 158 veterans and service members, found no significant effect on PTSD symptoms. The two Feder trials that generated most of the enthusiasm randomized 41 and 30 people respectively.
If it does not help PTSD, why offer ketamine at all?
Because depression and PTSD often travel together and the evidence differs. The VA/DoD depression guideline suggests ketamine as an augmentation option after several adequate medication trials have not worked, and in the largest PTSD trial depression scores improved while PTSD scores did not. That use is off-label and considered investigational by the FDA.
Would I be a candidate?
No article can answer that. It depends on your diagnosis, medical history, medications, substance use history, and what you have tried. Ketamine is Schedule III with recognized misuse potential, so those questions get asked carefully, and for many people the answer is no.
The bottom line
If you have wondered why nobody has offered you ketamine for PTSD, it is not that your clinician is behind the times. The guideline suggests against it, the randomized evidence is a few small trials plus one larger one that failed, and what benefit appeared faded within weeks. It still earns a conversation when treatment-resistant depression is the more disabling problem, and even then the target is the depression, that use is off-label and considered investigational by the FDA, and nobody can promise a response.
Talk with us
If you are in Fort Worth or the surrounding North Texas area and what you have read here sounds familiar, we would be glad to talk it through with you. The Institute for Advanced Psychiatry is an outpatient practice at 6800 Harris Parkway, Suite 100, treating adults 18 and older. You can request an appointment or call 817-659-7344.
If you are in crisis or thinking about harming yourself, please do not wait for an appointment. Call or text 988 to reach the Suicide & Crisis Lifeline, available 24/7, or go to your nearest emergency room.
Sources
- U.S. Department of Veterans Affairs and U.S. Department of Defense. “VA/DoD Clinical Practice Guideline for Management of Posttraumatic Stress Disorder and Acute Stress Disorder, Version 4.0.” June 2023. Recommendations 7, 8, 15, 18, 19, 20 and 24; Table 4 and the accompanying text on recommendation strength; Appendix E crosswalk of the 2017 recommendations. https://www.healthquality.va.gov/guidelines/MH/ptsd/
- U.S. Department of Veterans Affairs and U.S. Department of Defense. “VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder, Version 4.0.” February 2022. Recommendations 12 and 19. https://www.healthquality.va.gov/guidelines/MH/mdd/
- U.S. Department of Veterans Affairs, National Center for PTSD. “Medications for PTSD.” Accessed 2026-09-03. https://www.ptsd.va.gov/understand_tx/meds_for_ptsd.asp
- Feder A, Parides MK, Murrough JW, et al. “Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial.” JAMA Psychiatry 2014;71(6):681-688. https://pubmed.ncbi.nlm.nih.gov/24740528/
- Feder A, Costi S, Rutter SB, et al. “A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder.” American Journal of Psychiatry 2021;178(2):193-202. https://pubmed.ncbi.nlm.nih.gov/33397139/
- Abdallah CG, Roache JD, Gueorguieva R, et al. “Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial.” Neuropsychopharmacology 2022;47(8):1574-1581. https://pubmed.ncbi.nlm.nih.gov/35046508/
- Borgogna NC, Owen T, Vaughn J, et al. “So how special is special K? A systematic review and meta-analysis of ketamine for PTSD RCTs.” European Journal of Psychotraumatology 2024;15(1):2299124. https://pmc.ncbi.nlm.nih.gov/articles/PMC10791091/
- National Library of Medicine, DailyMed. “KETALAR (ketamine hydrochloride) injection, prescribing information.” Indications and Usage; controlled substance statement. Accessed 2026-09-03. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14e8f864-8b8a-4e7e-8439-e510d3107063
- National Library of Medicine, DailyMed. “ZOLOFT (sertraline hydrochloride) prescribing information.” Section 5.4, Screening for Bipolar Disorder and Monitoring for Mania/Hypomania. Accessed 2026-09-03. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fda754f6-d0f3-4dce-a17a-927d64f912f7
- U.S. Food and Drug Administration. “510(k) Premarket Notification database record K222101 (Prism, GrayMatters Health Ltd.),” including the cleared Indications for Use statement. Decision date 2023-03-17. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K222101
Medical disclaimer
This article is for general education and is not medical advice, a diagnosis, or a treatment recommendation for any individual. Reading it does not create a physician-patient relationship. Treatment decisions, including whether any medication or procedure is appropriate for you, should be made with a qualified clinician who knows your history. Do not start, stop, or change a psychiatric medication without talking to your prescriber. If you are experiencing a medical or mental health emergency, call 911 or 988.