INTRODUCTION — Posttraumatic stress disorder (PTSD) is a severe, often chronic and disabling disorder, which develops in some persons following exposure to a traumatic event involving actual or threatened injury to themselves or others. PTSD is characterized by intrusive thoughts, nightmares and flashbacks of past traumatic events, avoidance of reminders of trauma, hypervigilance, and sleep disturbance, all of which lead to considerable social, occupational, and interpersonal dysfunction.

Effective treatments for PTSD include psychotherapies and medications. However, a substantial proportion of patients have symptoms resistant to treatment. It is often necessary to switch or combine treatments to achieve a satisfactory therapeutic response.

This topic describes our approach to selecting treatment for PTSD in adults, which is also summarized in an algorithm (algorithm 1). The epidemiology, pathophysiology, clinical manifestations, assessment, diagnosis, psychotherapy, and pharmacotherapy for PTSD in adults are reviewed separately. Acute stress disorder and prevention of the development of PTSD, dissociative aspects of PTSD, and PTSD in children and adolescents are also reviewed separately.

●(See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis".)

●(See "Pharmacotherapy for posttraumatic stress disorder in adults".)

●(See "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults".)

●(See "Acute stress disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis".)

●(See "Dissociative aspects of posttraumatic stress disorder: Epidemiology, clinical manifestations, assessment, and diagnosis".)

●(See "Treatment of acute stress disorder in adults".)

●(See "Posttraumatic stress disorder in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)

●(See "Approach to treating posttraumatic stress disorder in children and adolescents".)

NEWLY DIAGNOSED PATIENT — Treatment for posttraumatic stress disorder (PTSD) should optimally be initiated shortly after diagnosis. The diagnosis of PTSD is made after persistence of symptoms for at least four weeks following the trauma, but most patients present for treatment many months, or sometimes years, later. In theory, early treatment of PTSD may prevent chronicity, but this not been shown empirically, particularly for pharmacotherapy [1].

First-line: Psychotherapy versus medication — For most adults newly treated for PTSD, we suggest first-line treatment with a trauma-focused psychotherapy that includes exposure rather than a serotonergic reuptake inhibitor (SRI). Psychotherapies found to be effective for PTSD in multiple clinical trials include exposure therapy (eg, prolonged exposure), a combination of exposure and a cognitive therapy (also referred to as trauma-focused cognitive-behavioral therapy [CBT]; eg, cognitive processing therapy), or eye movement desensitization and reprocessing [2-4].

An SRI is a reasonable alternative for patients who prefer medication to psychotherapy, or when CBT is not available. Multiple randomized clinical trials have found that patients with PTSD experience reduced PTSD symptoms when treated with an SRI compared with placebo [5]. Fewer randomized trials have found venlafaxine, a serotonin norepinephrine reuptake inhibitor, to be efficacious in PTSD [6,7]. (See 'Preference for medication' below and "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults".)

Comparative clinical trials suggest that SRIs and trauma-focused therapy with exposure, and the combination of the two modalities are largely comparably effective for PTSD [8,9], with some advantage to psychotherapy and to basing the choice between the two on patient preference.

●In a randomized preference trial of 200 patients with PTSD, participants were first randomized either to treatment of choice (sertraline or prolonged exposure) or randomized treatment assignment, and then either given their treatment of choice or randomized to treatment [8]. Efficacy of prolonged exposure and sertraline was, overall, equivalent across a range of outcomes, though some outcomes did favor prolonged exposure. There was a slight advantage (possibly mediated, in part, by better adherence) for patients who were randomized to their treatment of choice (irrespective of whether that treatment was prolonged exposure or sertraline), pointing to the importance of attending to patient preference in treatment selection.

●A clinical trial randomly assigned 207 patients with PTSD to receive sertraline plus enhanced medication management, prolonged exposure therapy plus placebo, or prolonged exposure therapy plus sertraline and followed for 24 weeks [9]. All groups experienced reduced PTSD symptoms, but groups did not differ in the magnitude of reduction among groups.

Choosing among therapies — Patient presentation can be influential in selecting among types of psychotherapy. For example, in individuals with extreme fear and avoidance, an exposure technique will likely be recommended. However, in individuals who are difficult to engage, virtual reality exposure might be chosen when available. Choosing among trauma-focused and non-trauma-focused therapies for individuals with PTSD is discussed further elsewhere. (See "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults", section on 'Non-trauma-focused psychotherapies and psychosocial interventions' and "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults", section on 'Choosing among trauma-focused therapies'.)

Co-occurring conditions — Subgroups of patients with PTSD may benefit from additional psychosocial treatment in addition to the first-line psychotherapy.

Substance use disorders — Patients with PTSD and an active substance use disorder can be treated with trauma-focused psychotherapy that includes exposure and substance use treatment simultaneously [10]. Current substance use does not necessarily require delay of psychotherapy for PTSD. (See "Psychotherapies for substance use disorders".)

Borderline personality disorder — Patients with co-occurring PTSD and borderline personality disorder may benefit from a psychotherapy treatment protocol that combines prolonged exposure and dialectical behavioral therapy, particularly if chronic suicidality and self-harm behaviors are prominent [11]. If no interfering behaviors are present (eg, self-injurious behaviors), prolonged exposure can be used initially, with dialectical behavioral therapy added as needed. (See "Psychotherapy for borderline personality disorder", section on 'Dialectical behavior therapy' and "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults", section on 'Exposure-based therapies'.)

Sleep disturbance, nightmares — For PTSD patients who experience significant sleep disturbance, most typically nightmares, we suggest treatment with prazosin, typically but not always augmenting first-line medication treatment with an SRI. Prazosin is taken 30 to 60 minutes before bedtime. Clinical trials of prazosin for sleep disruption in PTSD have found mixed results [12,13]. In our clinical experience, the medication reduces PTSD symptoms, nightmares, and sleep disturbance in approximately 50 percent of patients.

Psychosis — SRIs are typically first-line medications in treating PTSD. In PTSD patients with comorbid psychotic symptoms, we suggest augmenting SRI treatment with an antipsychotic medication [14]. (See 'Preference for medication' below and "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Second-generation antipsychotics'.)

TREATMENT RESPONSE

Robust — Patients who respond favorably to a serotonergic reuptake inhibitor (SRI) should continue to take it for at least six months to a year to prevent relapse or recurrence [15]. Treatment gains are generally maintained following effective psychotherapy with an evidence-based treatment for posttraumatic stress disorder (PTSD) [16]. (See "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Duration of treatment' and "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults".)

Poor or partial — If a therapeutic dose of psychotherapy (eg, eight sessions) has been delivered and the patient has truly engaged in the therapy, following all of the therapist’s recommendations, but has not responded sufficiently, a change of course is needed:

●Following a poor response, a switch to another trauma-focused psychotherapy that includes exposure, to an SRI, or to a combination of both modalities.

●Following a partial response, augmentation with another trauma-focused psychotherapy that includes exposure, to an SRI, or to a combination of both modalities.

The choice among psychotherapy, medication, and their combination in patients who experienced a poor or partial response to initial treatment can be made on the basis of treatment availability and/or patient preference. There are no clinical trials comparing medication with psychotherapy in PTSD patients who do not response to initial treatment.

Preference for psychotherapy — The type of added psychotherapy may be suggested by the patient’s clinical presentation. As an example, if a patient is not able to engage emotionally with the trauma memory and reminders, or refuses to engage, a change from exposure therapy to a combined cognitive therapy/exposure therapy approach might be useful. (See "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults".)

Assessment results can inform subsequent treatment decisions. As an example, the Emory Treatment Resistance Interview for PTSD can be used to systematically assess the patient’s treatment history (including whether therapeutic doses were received), his or her current clinical status and treatment preferences [17].

Preference for medication

Second-line — For patients who have a poor or partial response to psychotherapy and do not want a trial of another trauma-focused psychotherapy that includes exposure, we suggest second-line treatment with an SRI (either a selective serotonin reuptake inhibitor [SSRI] or venlafaxine, a serotonin norepinephrine reuptake inhibitor [SNRI]) rather than other medications.

Clinical trials comparing the combination of an SRI and cognitive-behavioral therapy with either modality as monotherapy have found no difference in sustained improvement between groups [18]. These trials did not look specifically at augmenting treatment with an additional modality in patients who did not respond to initial monotherapy. In our clinical experience, we have found that some patients treated with an SRI or trauma-focused psychotherapy that includes exposure benefit from the addition of the second modality after a poor response to the first. (See "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Serotonin reuptake inhibitors (SRIs)' and "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Drug augmentation of psychotherapy'.)

Clinical trials have not compared the efficacy of different medications for PTSD. Multiple clinical trials have found SSRIs to reduce PTSD symptoms compared with placebo [5]. Venlafaxine, an SNRI, has also been found to be efficacious in PTSD compared with placebo [6,7], although it has been less extensively studied compared with SSRIs.

The administration, dosing, and side effects of SRIs are reviewed separately. (See "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Serotonin reuptake inhibitors (SRIs)' and "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects", section on 'Side effects' and "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management".)

Third-line — For patients who do not respond to the SRI after 8 to 10 weeks at the highest tolerated dose in the therapeutic range and do not want a trial of a trauma-focused psychotherapy that includes exposure, we would proceed to a trial of a different SRI.

Fourth-line — For PTSD patients treated with medication who fail to respond to two SRI/SNRI trials and do not want a trial of a trauma-focused psychotherapy that includes exposure, we suggest treatment with a second-generation antipsychotic medication. For patients with a minimal response to an SRI, we favor monotherapy with quetiapine; if a partial response, we favor augmentation with quetiapine or risperidone. (See "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Second-generation antipsychotics'.)

Clinical trials support treating PTSD with second-generation antipsychotics as monotherapy [19]; in addition, add-on treatment can reduce reexperiencing and hyperarousal symptoms [20]. However, the evidence of their efficacy is weaker compared with that supporting SRIs, and with a greater potential side effect burden (eg, weight gain, dyslipidemia, hypertension, and/or hyperglycemia) (table 1). Based upon the absence of other medications proven to be effective and our clinical experience that some patients appear to benefit from second-generation antipsychotics, they are an option for patients failing previously suggested treatment. (See "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Second-generation antipsychotics' and "Second-generation antipsychotic medications: Pharmacology, administration, and side effects".)

SUMMARY AND RECOMMENDATIONS

●Our approach to selecting treatment for posttraumatic stress disorder (PTSD) is summarized in an algorithm (algorithm 1).

●For adults newly treated for PTSD, we suggest first-line treatment with a trauma-focused psychotherapy that includes exposure rather than a serotonergic reuptake inhibitor (SRI) (Grade 2C). An SRI is a reasonable alternative for patients who prefer medication to psychotherapy, or when a trauma-focused psychotherapy including exposure is not available. (See 'First-line: Psychotherapy versus medication' above and "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults".)

●Trauma-focused psychotherapies that include exposure have been supported by multiple clinical trials in adults with PTSD and include exposure therapy (eg, prolonged exposure), a combination of exposure and a cognitive therapy (also known as trauma-focused cognitive-behavioral therapy; eg, cognitive processing therapy), and with eye movement desensitization and reprocessing. (See 'First-line: Psychotherapy versus medication' above and "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults".)

●A patient presentation with extreme fear and avoidance favors the use of an exposure technique, while presentation with extreme guilt and trust issues favors cognitive therapy or exposure therapy. For patients who are difficult to engage emotionally, virtual reality exposure could be added where available, as its evocative nature renders it more difficult to avoid. (See 'First-line: Psychotherapy versus medication' above and "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults".)

●PTSD patients with a co-occurring substance use disorder or borderline personality disorder may benefit from treatment with a combination of trauma-focused psychotherapy that includes exposure and substance use treatment or dialectical behavioral therapy, respectively. (See 'First-line: Psychotherapy versus medication' above and 'Co-occurring conditions' above and "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults".)

●For PTSD patients who experience significant sleep disturbance, most typically nightmares, we suggest treatment with prazosin 30 to 60 minutes before bedtime (Grade 2C) rather than other medications. (See 'Sleep disturbance, nightmares' above.)

●Patients who respond favorably to an SRI should continue to take it for at least six months to a year to prevent relapse or recurrence. (See 'Robust' above and "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Duration of treatment'.)

●For patients who have not improved after eight or more sessions with a particular psychotherapy, we favor second-line treatment with augmentation or switching to another trauma-focused psychotherapy that includes exposure or an SRI. The choice between psychotherapy and medication as second-line treatment can be made based on treatment availability and/or patient preference. (See 'Poor or partial' above.)

●For patients who have a poor or partial response to psychotherapy and prefer to switch to or add a medication, we favor second-line treatment with a SRI rather than other medications. (See 'Second-line' above and "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Serotonin reuptake inhibitors (SRIs)'.)

●For patients who do not respond to the SRI after 8 to 10 weeks at the highest tolerated dose in the therapeutic range and do not want a trial of a trauma-focused psychotherapy that includes exposure, we favor a trial of a second SRI rather than other medications. (See 'Third-line' above and "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Serotonin reuptake inhibitors (SRIs)'.)

●For PTSD patients treated with medication who fail to respond to two SRI trials and do not want a trial of a trauma-focused psychotherapy that includes exposure, we treat with a second generation antipsychotic rather than other medications. For patients with a minimal response to an SRI, we favor monotherapy with quetiapine; if a partial response, we favor augmentation with quetiapine or risperidone. (See 'Fourth-line' above and "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Second-generation antipsychotics'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Barbara Rothbaum, PhD, who contributed to an earlier version of this topic review.