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      QUEST - Posttraumatic Stress Disorder  

 

AUTHOR
 Sampath Kumar 

Intimate Partner Violence

Chairman’s Rounds, January 29, 2007

Reference: Miriam K. Ehrensaft, Terrie E. Moffitt, and Avshalom Caspi Am J Psychiatry 2006; 163: 885-92.                                                                                       

Clinical Question:  Does intimate partner violence lead to increased mental illness?  Is there a difference based on gender? 

Clinical Case or Background Info: Phone call from wife of a veteran to commit patient over the phone as he was threatening to hurt her. Wife was asked to petition vet. Vet “broke all things breakable in my house before he got to the hospital” according to wife. 

Question Type: Predicting harm. 

Validity Criteria: Both groups were treated equally and assessed at the same intervals, follow-up was not complete: there were 1037 to start, so follow up was 90% at age 18 and 95% at age 26.  However, this is remarkably good for a study lasting 23 years! This rate of follow-up, although not complete, should be sufficient to meet validity criteria. There is a reasonable temporal relationship between exposure and outcome.

Study Design Type: Longitudinal Cohort Study

Sample: cohort of 1,037 children (52% boys, 48% girls) was constituted at age 3, 91% of consecutive births, April 1972 and March 1973 in Dunedin, New Zealand. Across all socioeconomic status.

 

Assessment:

Diagnostic interview Schedule was used at both points. Depression, Alcohol dependence, MJ dependence was analyzed at 18 &26. Anxiety disorders at 18 were analyzed with PTSD at 26. Abuse was measured with Partner Conflict Calendar which was laid beside Life history Calendar to cue memories. 

Analysis: Hierarchical Logistic regression modeling. Separate models for men and women, and for each disorder studied. : Psychiatric disorder at 26 was regressed onto same disorder at 18, juvenile conduct disorder, and abuse between 24 and 26

Main Results: 

I- Adolescents with a history of mental illness have a higher chance of getting into abusive relationships.

II- Men and women reported equal mean numbers of events in the clinical abuse group

III- In women aged 26 years, even after correcting for previous diagnosis of the same disease and lifetime conduct disorder, being in an abusive relationship within the last 3 years

1)       Increases the odds of having a depressive disorder by 2.46 times

2)       Increases the odds of being dependant on Marijuana by 10.14 times

3)       Increases the odds of having PTSD by 6.42 times

However, in men aged 26 yrs, being in an abusive relationship does not seem to predict an increase in the odds of having a mental illness after correcting for past history of the same mental illness and lifetime conduct disorder. Please refer to table 1. 

Limitations: Recall bias, the range of age in the group is small and minor cases of abuse were not included.

Conclusions:  

Partner abuse contributes to increase in psychiatric morbidity among the reproductive age group in women. Though one of the explanations for  increase prevalence of abuse among mentally ill people was that patients with mental illness are more prone to getting involved in abusive relationships (which is also shown in this study), by establishing a temporal relationship between the exposure and event, this study also shows that abuse can also cause an increase in psychiatric illness

Teaching Point:  Asking about intimate partner abuse in psychiatric patients will help one pick up important etiological information and intervention by abuse prevention might alter the prognosis of the illness. 

Table 1 

 

Risk factors predicting disorder at age 26 after regressing abuse, past history of same disorder, & conduct disorder (CD); odds ratios in parenthesis

Disorder 

Women

Men

Major depressive episode (MDD)

MDD at 18   (1.93**)

Abuse (2.46*)

MDD at 18 (3.38**)

Marijuana dependence (MJ)

MJ at 18 (10.26**)

CD (3.36*)

Abuse (10.14**)

MJ at 18 (3.72**)

CD (4.44**)

Alcohol dependence (ETOH)

ETOH at 18 (3.45**)

CD (4.09**)

ETOH at 18 (3.47**)

CD (1.78*)

Post-traumatic stress disorder (PTSD)

Abuse (6.42**)

Anxiety disorder at 18 (3.04*)

CD (3.15*)

Generalized anxiety disorder (GAD)

___

 

GAD at 18 (2.90*)

* p<0.05

** p< 0.01

Sites that give information about sources for referring patients in abusive relationships:

http://www.nccadv.org/ or http://durhamcrisisresponse.org/

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AUTHOR
Harold Hong

Brief CBT Treatment of Acute PTSD

Chairman’s Rounds, January 29, 2007

Reference:  Sijbrandij, Marit et al.  Treatment of Acute Posttraumatic Stress Disorder with Brief Cognitive Behavioral Therapy: A Randomized Controlled Trial. American Journal of Psychiatry.  164:1, January 2007. 

Clinical question:

Background And Objectives: Persons that experience trauma carry considerable risk of developing PTSD.  Various efforts have been made to evaluate the hypothesis that psychological intervention in the early post-traumatic period can prevent the development of PTSD.  However, results thus far for various interventions have been somewhat mixed – with studies showing both positive and negative outcomes.  This particular study was designed to test the hypothesis that a brief course of therapy tailed around cognitive-behavioral principles444

Methods:

Design / Setting – Randomized control trial in an academic clinic setting

Patient Population – predominantly Dutch, HS level of education, and had previously experienced another trauma.

Inclusion Criteria – 1. Met dx criteria for acute PTSD (DSM-IV, minus time criterion), 2. Trauma occurred between 2wks and 3 months prior to inclusion 3. Traumatic event is finished at time of inclusion 4. 18 yrs old or greater 5. Proficient in Dutch

Exclusion Criteria – 1. Presence of SI  2.  Meet dx criteria for a psychotic disorder, organic disorder, substance abuse, or chronic PTSD

Enrollment method – Trauma victims were referred from the community care setting

Number screened vs. Number enrolled –278 screened, 143 enrolled (102 did not meet inclusion criteria, 135 met exclusion criteria, 33 refused)

Intervention – CBT format adapted from CBT for female victims of rape by Foa et al.  There were four 120 minute sessions spaced 1 wk apart.  Session 1 – information gathering, education, and noting of cognitive distortions, and situations that were avoided.  Session 2  - list of avoided situations completed and ranked by degree of anxiety caused by each situation, and deep muscle relaxation exercises practiced and audio taped for homework, use of imaginal exposure audio taped, discussed cognitive distortions.  In-between sessions 2 and 4, pt’s told to relive the experience by listening to tapes of imaginal exposure and confront avoided, but safe, situations.  Session 3 – review of homework assignment, imaginal exposure, and cognitive restructuring. Session 4 – homework reviewed, imaginal exposure and cognitive restructuring, discuss progress of the patient.

Control – assessed at same follow-up times as the patients.  Pt’s then referred to therapy if found to meet criteria for PTSD.

Analysis – intention to treat

Primary Outcomes – Pt’s assessed at baseline, 1 week, and 4 months.  PTSD sx severity was measured via Structured Interview for PTSD

Secondary and Additional Outcomes –  Hospital Anxiety and Depression Scale scores, SCID-I for dx of co-morbid axis I disorders  pt satisfaction with CBT group. 

Validity: Randomized?  Yes

Blinding – randomization was blinded. 

Treatment groups similar at baseline? Yes, no significant differences between intervention and control groups

Patients starting trial accounted for at conclusion?  Yes

Patients analyzed in groups to which they were randomized?

Intention to treat analysis? yes

Patients and clinicians blinded to treatment? Not explicitly stated if assessors were blinded

Groups treated similarly outside of intervention? Yes

Results
 Primary outcomes –  Structured Interview PTSD scores significantly lower at week 1 compared to control group (total, re-experiencing, hyperarousal).  However, there were no significant differences in Structured Interview PTSD scores between treatment and control groups at 4 months follow up.

Additional outcomes – there were no significant differences between groups on Hospital Anxiety and Depression Scale scores.

There were significant differences between rate of diagnosis of PTSD at week 1 and follow-up – 38.1% in Tx group 61.1% in control, and then 26.4% in Tx group and 43.8% in control group at 4 months. 

Adverse effects – none reported 

Comments
Strengths: This study has a considerable sample size. This study evaluates a specific area of PTSD treatment

Weaknesses: No power calculations were stated regarding subgroup analysis.  Exclusion criteria of those that have co-morbid substance abuse marks out a particular subset of PTSD pt’s

Next steps for further study: study of brief courses of CBT involving different methods than the ones employed here.  Study of brief courses of CBT for the treatment of non-civilians 

CLINICAL BOTTOM LINE: A brief course of CBT can be helpful in reducing symptom severity in the short term following trauma, however, it has not been shown to reduce symptom severity in the longer term (4 months).

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AUTHOR:
Victoria Carroll

Efficacy And Tolerability Of Mirtazapine And Sertraline In Korean Veterans With Posttraumatic Stress Disorder

Chairman’s Rounds, November 20, 2006

Reference: Chung, MY et al.  Efficacy and tolerability of mirtazapine and sertraline in Korean veterans with posttraumatic stress disorder: A randomized open label trial.  Hum Psychopharmacol Clin Exp 2004; 19:489-494.

Clinical Question: In terms of efficacy and tolerability, how does mirtazapine compare to sertraline in the treatment of combat veterans with Post Traumatic Stress Disorder? 

Background: 30.9% of male and 26.9% of female Vietnam veterans in the U.S. have PTSD.  The medication mirtazapine increases both noradrenergic and serotonergic signaling by its antagonism at central presynaptic α2-receptors.  The resultant
increase in serotonergic signaling affects primarily 5HT1 receptors, as mirtazapine antagonizes 5HT2 and 5HT3 receptors.  This 5HT2 and 5HT3 antagonism is thought to result in mirtazapine’s anxiolytic and pro-sleep effects, as well as its lower incidence of serotonin-induced side effects. 

Question Type: Therapy

Validity Criteria: Complete follow-up? All subjects were accounted for, with 13 patients dropping out of the study (reasons given for dropouts).  Randomized?  Yes, but it is unclear if randomization was concealed.  Intention to treat: Subjects were analyzed in the groups they were randomized to; data from subjects who dropped out were not analyzed.  Similar groups?  Please see Tables 1 & 2, p. 491.  The groups appear quite similar, but the mirtazapine group (M group) had more subjects with a h/o hospitalizations and suicide attempts, though this may not have been statistically significant.  Blinding?  This was an open-label study; it is unclear whether analyzers were aware of subjects’ allocations.  Equal treatment?  Yes.

Study Design: Randomized, open label trial; funded by a grant from Organon and Janssen.

Duration: 6 week study

Setting: Seoul Veterans Hospital

Population: 113 veterans of the Korean or Vietnam Wars (95 outpatient and 18 inpatient) with PTSD and possible comorbid depressive d/o (if depressive sx for > 3 months).  It is unclear how many subjects were enrolled.

Intervention: Subjects were randomized to receive either mirtazapine (n=51) or sertraline (n=49).  After a 7-day washout period, subjects were started on mirtazapine 15 mg qd or sertraline 50 mg qd; doses could be adjusted after weeks 1, 2 and 6. 

Outcomes: Outcome measures were not explicitly stated.  Subjects in each group were identified as “responders” or “nonresponders” based on improvement as measured by clinician administered PTSD scale (CAPS-2), the Hamilton rating scale for depression (HAMD-17) or the clinical global impression scale (CGI), each measured at baseline and weeks 1, 2 and 6.  A psychiatrist assessed side effects through “direct inquiry.”

Results: See Tables 3 and 4 (over).

--Statistically significant reductions (vs. baseline) in CAPS-2, HAMD-17, and CGI in both groups at week 6.  The differences b/t both groups in these reductions were not statistically significant.

--CAPS-2 Total: 43.4% in M group v. 37.4% in S group (p=0.467)

--CAPS-2 Clusters: Reductions from baseline to week 6 were similar in both groups

--HAMD-17: 58.5% in M group v. 59.1% in S group (p=0.319)

--CGI-S: 49.2% in M group v. 49.2% in S group (p=0.809)

--Percentage responders, as measured by:

            CAPS-2: statistical significance by week 6 (88.24% in M group v. 69.39% in S group, p=0.039)

            HAMD-17: no statistically significant difference b/t groups at weeks 1, 2 and 6

            CGI-S: ?trending toward intergroup difference by wk 6 (96.08% in M gr v. 87.76% in S gr, p=0.156)

 

Risk of CAPS2 Response*

RR of CAPS2 Response

Risk of HAMD-17 Response

RR of HAMD-17 Response

Risk of CGI-S Response

RR of CGI-S Response

Mirtazapine

45 / 51 = 0.88

0.88 / 0.69 = 1.28

38 / 51 = 0.75

0.75/0.78=0.96

49 / 51 = 0.96

0.96/0.88=1.10

Sertraline

34 / 49 = 0.69

 

38 / 49 = 0.78

 

43 / 49 = 0.88

 

*Risks calculated in this table are from data collected at 6 weeks. 

Comments: This 6-week study found that a group of Korean combat veterans with PTSD treated with mirtazapine (vs. sertraline) had a higher proportion of responders as measured by the CAPS-2.  There were no differences between groups in magnitude of improvement as measured by the CAPS-2, CGI-S, and HAMD-17 scales; both groups did, however, show significant improvement on all scales from baseline to week 6.  Strengths: study assessed both PTSD and depressive sx; study directly compares two interventions.  Weaknesses: short duration of study (would some of the differences observed extinguish or increase with time?; if mirtazapine has been noted to have a shorter time of onset, does that bias the results because of the short duration of the study?); study was designed so subjects could have comorbid depressive dx, but all the subjects in this study didàhow would the results vary (e.g. on the HAMD-17) in subjects without a depressive dx?; the M group had higher scores on the scales at baseline—how did this affect the results (e.g. is it easier to show response with more severe pathology than it is less severe?); study was sponsored by manufacturer of mirtazapine; small population size.         

Bottom Line: In a 6-week randomized, open label trial involving 61 Korean combat veterans with PTSD, a higher proportion of subjects receiving mirtazapine responded to treatment as measured by the CAPS-2 than subjects receiving sertraline; there was no difference in the proportion of responders as measured by the HAMD-17 and CGI-S.  There were also no differences between groups in magnitude of symptom improvement as measured by the CAPS-2, HAMD-17, and CGI-S, though both groups did show significant improvement on all scales from baseline to week 6. 

 

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AUTHOR:
Seamus Bhatt-Mackin

Comparison of Sertraline And Placebo In The Treatment Of PTSD

Chairman’s Rounds, August 7, 2006

Citation:   Multicenter, Double-blind Comparison of Sertraline and Placebo in the Treatment of PTSD. Davidson et al.   Archives of General Psychiatry   May 2001, Vol 58 pp. 485-92.  

Clinical Question:  Compared to placebo, is sertraline an effective acute treatment for PTSD?

Clinical Case or Background Info:  It is routine in PEC to start patients with PTSD on SSRIs and the word on the street suggests that setraline has the best evidence for such practice.

Question Type:  Therapy

Validity Criteria:

Follow-up: unclear

Randomization:  pts were randomized, method not described

Intention to treat: claimed in methods section, but unclear

Similar groups: yes, except for small difference in percentage of women

Blinding: not well described (“double-blind” likely refers to patients and clinicians, but not made explicit and also treating clinicians = assessors?)

Equal treatment: both groups had same treatment throughout trial

Study Design Type:  Randomized Controlled Trial

Allocation:  randomized (no description of method)

Blinding:  double-blind

Follow Up Period:  12 weeks

Setting:  outpatient clinic

Patients/Population:  ~80% women, ~80% white, ~age 36, ~60% physical or sexual assault as traumatic event, ~25% hx alcohol dependence,

Intervention/exposure:  treatment with flexible-dose sertraline 50-200mg

Primary Outcomes:  responder 30% decrease in score on CAPS-2 (Clinician Administered PTSD Scale), IES (Impact of Event Scale), CGI-S (Clinical Global Impression-Severity Scale)

Patient Follow Up: not well described (see Follow-up above)

Main Results:  There is a specific treatment effect of sertraline (60% responder rate on CAPS-2)  that distinguishes it from the placebo arm (38% responder rate) with a number-needed-to-treat of 4. 

Conclusions: Unfortunately, the patient characteristics in this study do not match well with the patient population at the DVAMC.  There is a significant difference between treatment with sertraline and the placebo arm, demonstrating a specific effect of the medication.  This study will not change my current clinical practice. 

Two Teaching Points: 

1)  Nonspecific effects of treatment are powerful in the treatment of this illness (as demonstrated by the 38% responder rate in the placebo arm of the trial), but also note visits at weeks 1, 2, 3, 4, 6, 8, 10 and 12.

2)  Response in this study was defined as a 30% decrease on CAPS-2 scale; does this represent improvement in level of function?  Is this a clinically significant improvement?

Two Questions for Discussion:

1) 70% of the improvement in PTSD symptoms occurred during the first 4 weeks of treatment (we don’t know how the dosage was titrated).  Is that consistent with attendings’ clinical experience?  Do PTSD symptoms consistently respond like this?

2) In schizophrenia, cognition matches better with functional outcome than the diagnostic symptoms of the illness.  Is there a clear relationship with a particular symptom or aspect of PTSD and level of function? 

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VIRTUAL REALITY EXPOSURE TREATMENT FOR VETERANS WITH PTSD

Author:
Rosario Hidalgo, MD

Bottom Line: Virtual reality exposure (VRE) may represent a useful adjuvant treatment for veterans suffering from chronic PTSD.

Background: VR integrates computerized devices to immerse a participant in a computer generated visual environment. VRE has showed to be effective in treatment of specific phobias (i.e. flying, heights, etc). In this paper VRE is proposed as an alternative to typical imaginal exposure treatment for Vietnam combat veterans with PTSD.

Search terms: PTSD, virtual reality, therapy.

Clinical case: 48 yo 100% service connected (PTSD) AAM with chronic severe PTSD who has hx of poor response to numerous antidepressants. Pt is currently taking Fluoxetine 80mg po qd but continues to experience daily intrusive memories, weekly flashbacks and chronic insomnia due to frequent nightmares about his Vietnam experiences. Pt would like to know if there is something else he could try to ease his sxs. 

Reference: Rothbaum BO et al. Virtual reality exposure therapy for the Vietnam veterans with PTSD. J Clin Psychiatry 62:617-622.

Methods: open clinical trial. Conducted at the Atlanta VA hospital on an outpatient basis. (N=16; Male veterans). Inclusion crit: chronic PTSD, treatment refractory pts who are able to provide informed consent, and have enrollment approval from treating physicians. Exclusion crit: current substance addiction, serious heart condition, psychosis, bipolar d/o, unstable medication regimen (in the past 3 mo), planned departures from the Atlanta area, uncontrolled suicidal intention. Pts were recruited using publicity and referral resources. 31 pts were screened and 16 pts were enrolled.

Intervention: 8 to 16, 90min sessions conducted twice weekly over 5-7 wks.

Analysis: authors didn't specify which statistical models they used. There was no intent-to-treat analysis; authors included only the data from the 9 participants who completed the treatments and post-treatment f/ups.

Outcomes: % change in different scales used (CAPS: clinician administered PTSD scale (primary); IES: impact of event scale; BDI: Beck depression inventory).

Follow up: authors evaluated pt pretreatment, after completion and did a 3 and 6 months f/u eval. At 3 months f/u only 5 pts were evaluated and at 6m 8pts participated of the f/u. Authors did not account for the lost to f/u.

Validity: limited by the fact that is a small open trial, group of pt may be not completely homogeneous (they had different comorbidities, were taking different medications, etc). However, the study population pretty much resembles the characteristics of our pt and many pts we may encounter at the VA. 

Results:
For 1ry outcomes: CAPS. There was an overall statistically significant reduction from baseline (from 15% to 67%) at 6 mos. This decrease was seen in all 3 symptom clusters of PTSD.

2ry outcomes: IES. Pt self reported intrusion symptoms were significantly lower at 3 months than at baseline but not at 6 mo, although there was a trend towards fewer intrusive thoughts and somewhat less avoidance. BDI. There was a statistically significant reduction at 6 mos. There were no adverse effects reported.

Comments:
The strengths of the study are related to the fact that this is a treatment that is feasible with just minor equipments and can be done in an office setting. Another clear strength is the fact that the population treated is very similar to many of the pts that we see at the VA, although pts with current substance abuse and serious medical conditions were excluded.

The major weaknesses of the study are being non-controlled, open label and with a very small sample. Other weaknesses are that the authors didn't account for pts lost to follow up and did not do an intent to treat analysis. Not all the pts were treated equally (while standard treatment was 10 sessions, some pts received 8 and another 16). There are other factors that can also act as confounders (i.e. pts were taking different medications in non-reported doses for an unknown total time, were seeing their doctors, etc and all these interventions may affect the outcome). Another possible confounder is the fact that the l' two authors disclosed that they share sales royalties in one of the companies who provided the equipment for VRE.

Regardless these limitations, VRE may still be a useful component of a comprehensive treatment program for severe cases of PTSD. There is need for controlled studies and the authors reported that there is one currently underway at the VA Nat Ctr for PTSD in Boston, Mass.

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BENZODIAZEPINES IN THE TREATMENT OF PTSD

Author:
Julie Adams, MD

Bottom Line: The use of benzodiazepines in the treatment of PTSD shows no significant improvement of outcome in recent trauma survivors when compared to no pharmacotherapy.

Background: Up to 94% of recent trauma survivors will experience PTSD symptoms in the first week post trauma. Most patients will experience remission of symptoms over 9 months, but between 15% and 25% will be left with a pervasive disorder.

Clinical Question: Can early use of benzodiazepines in recent trauma survivors prevent development of chronic PTSD?

Reference: Gelpin E, Bonne 0, Peri T, Brandes D, Shalev A. "Treatment of recent trauma survivors with benzodiazepines: a prospective study," J Clin Psych 57:9, September 1996.

Methods: Subjects recruited for this study were all admitted to an ED following a traumatic event. Those who met DSM-III-R PTSD Criterion A were invited for inclusion. Those who were currently taking psychotropics were excluded, as were those with head injury, coma or loss of consciousness. Of 162 subjects, only 13 were started on a benzodiazepine (10 with clonazepam, 3 with alprazolam) based on evaluation of symptoms. All used the medication for at least a month and 9 used medication for the study duration. Those in the treatment group were matched with 13 controls based on gender and initial Horowitz Impact of Event Scale (IES) score. At the initial interview, subjects were assessed using the IES, the Spielberger State-Trait Anxiety Inventory (STAI-State), and the Beck Depression Inventory (BDI). Interviews at the 1- and 6-month follow up included, in addition, the Mississippi Rating Scale for Combat-Related PTSD-civilian trauma version (MISS), the Structured Clinical Interview for DSM-III-R (SCID) and the Clinician Administered PTSD Scale (CAPS). Resting heart rate was also measured.

Validity: The subjects in this study were not randomized and not blinded to their treatment. Likewise the controls were not blinded. The interviewer "was not involved with clinical management" but it is unclear from the article if this meant the person was blinded. The psychiatrist who prescribed benzodiazepines was blinded to the patients' psychometric scores.

Results: ANOVA showed a significant main effect of time for STAI (F=4.8, df=2,24; p<.03) and MISS (F=4.8, df=1,25; p<.04) and no other statistically significant effects. At the 6-month follow up 9 subjects in the treatment group (69%) and 2 controls (15%) met CAPS-PTSD diagnostic criteria.

Comments: Rates of PTSD were higher in the treatment group than in either the control group or the larger study group. Rates between the controls and larger study group did not differ significantly. A possible explanation could be that those treated were sicker at baseline and therefore possibly at greater risk for developing PTSD in the first place. And while treatment may have improved their symptoms, it did not prevent development of PTSD in 69% of these patients. Another explanation could be that early treatment with benzodiazepines might actually worsen outcome. While benzos are theorized to inhibit memory acquisition, the effect is anterograde. Given after the fact, benzos could interfere with adaptation, reappraisal and learning which could be helpful in recovery. While this study is clearly flawed, the results are still alarming.

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RISK FACTORS FOR DEVELOPING PTSD AFTER TRAUMA EXPOSURE

Author:
Heidi Harrom, MD

Clinical Question: What factors may predict the likelihood for developing PTSD in a patient who has been exposed to a trauma?

Citation: Brewin, CR, Andrews, B and Valentine, JD. Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. Journal of Counseling and Clinical Psychology 68(5):748-766,2000.

Clinical Bottom Line: Certain risk factors are shown consistently to predict PTSD but to varying extents, others with more demonstrated homogenous effects, and those that seem to predict PTSD in some populations only. Factors operating during or after the trauma appear to show more effect than pre trauma factors.

Search Methods: The evaluators used bibliographic databases, recent journal articles, review articles, and book chapters. The Social Science Citation Index and PILOTS databases were searched using the words PTSD and risk, predictor, prediction, or predisposition.

General Methods: English-written studies from 1980-present which analyzed predictive or risk factors for PTSD were searched, excluding those which didn't assess avoidance/arousal/re experiencing sx, those that included both fully dx PTSD and "partial" PTSD subjects, those whose subjects all already had PTSD or other Ψ sx, those studies which didn't report analysis of all pts exposed to similar adulthood trauma, and those with insufficient data to calculate relevant effect size. 77 articles were ultimately selected. Risk factors that were studied in 4+ articles were analyzed, which included 14 factors. Researchers then looked at the impact that certain study/sample characteristics may have on risk factor effect sizes (military vs civilian, gender, study design, analysis based on diagnosis vs continuous sx scores, interview vs. questionnaire, presence of childhood or adult trauma vs adult only). Regardless of statistical design used in original studies (t(F/chi­square in group designs or Pearson's r/Spearman's P in co-relational studies), these were converted to correlation coefficient r for a common measure for effect size, then combined using Fisher's Z transformation and converted back to r for a weighted average effect size. Higher r values indicate a stronger positive association of a factor with PTSD.

Validity: A focused clinical question was addressed and inclusion criteria was appropriate. The authors specifically analyzed the potential effect an omitted relevant study may have on their conclusion . Separate analysis was performed for those study/sample characteristics which could possibly skew results. Interrator reliability was stated as high. The degree of heterogenicity between the included studies was notable and could indicate that the risk factors don't always predict equally well. Details about the included studies were not sufficient to determine certain characteristics such as follow-up.

Comments: The study had access to a large sample size and made effort to control for the effects of certain study/sample characteristics on the studies. There were too many studies included for detailed data regarding individual studies. Results are comprehensive and factors generally consistent predictors, but only certain characteristics were found to be homogenous. Attempts to identify a common set of pre trauma predictors valid across groups may be premature. Unclear at this point why civilian women are at greater risk for PTSD. Not enough prospective studies. Many pre trauma predictors may not be independent of each other.

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PREVENTION OF SECONDARY PREVENTION OF POSTTRAUMATIC STRESS DISORDER WITH PROPRANOLOL

Question: In a patient who presents to the emergency room after a traumatic event, does administration of a centrally-acting B-blocker prevent subsequent development of post-traumatic stress disorder? (Pre clinical studies have shown that epinephrine strengthens memory consolidation and fear conditioning; and, propranolol abolishes this effect-)

Pilot study of secondary prevention of post-traumatic stress- disorder with propranolol. Pitman, RK et al. BiologicalPsychiartry, 2002. Vol 51, pp 189-142.

Study: 41 emergency room patients who had just experienced a-traumatic event then received a 3-week course of either propranolol or placebo. Patients were assessed for PTSD at 1 and at 3 months post-trauma, using a clinician administered PTSD scale. Also at 3 months, a "psychophysiological"assessment was done: patients listened to a taped script (in their own words) describing the trauma and were asked to imagine the event for 30 seconds while HR, skin conductance, and EMG responses were measured.

Validity:
Randomization- Patients were randomized to either study group.
Follow-up- The attrition rate was high, particularly in the treatment group. This loss was not accounted for. (Of 18 propranolol patients, 50% dropped out by the end of the study; only I I completed the 1-month assessment and only 9 completed the 3-month assessment. Of 23 placebo patients, about 35% dropped out; only 20 completed the 1-month assessment and only 15 completed the 3-month assessment. Only 8 propranolol and 14 placebo patients completed the physiological measure.)
Analysis- Patients were analyzed in the groups to which they were randomized.
Blinding- A blinded clinician assessed the patients. A separate research nurse provided supportive counseling and monitoring of medication side effects.
Baseline characteristics- Groups were similar at the start of the trial. There were no significant differences in: overall percentage of trauma due to MVA, sex, age, self-rated response intensity, time to first dose of medication, and heart rate in the ED.
Treatments- Aside from the treatment intervention, the two groups night NOT have been treated equally. The paper does not report contact with the research nurse, and the authors suggest that perhaps the treatment group had more contact secondary to having had more side effects.

Results:
The most statistically significant result was at the one month assessment: 9 (out of 11) of the propranolol patients had scores below the median for treatment group, p=.03. 

How does this apply to the patient?
It is difficult to tell whether these patients are comparable to those we see in the ED. Not much detail is given about patient characteristics other than sex (about half male, half female), mean age (about 34), and the fact that 70% of the traumas were due to MVA.

As for the treatment outcomes measured, one thing to note is that the psychophysiological measure is correlated with PTSD in a previous lab study, this measure is not used clinically. Furthermore, the B blocker may be affecting physiology apart from any psychological effect, ie just because the propranolol group has for example, less reactive heart rates, does not mean that this is because they don't have PTSD -- it could be a direct physiological effect of the medication.

The most concerning flaw of this study is that the treatment dropouts were not accounted for in the statistics. Given the very high attrition rate in the treatment group, and the potential side effects, I would not use propranolol for prevention of PTSD.

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PHARMACOTHERAPY FOR TREATMENT OF PTSD

Author:
Sandeep Vaishnavi, MD

Bottom Line: In a systematic review of 13 RCTs of pharmacotherapy for PTSD, the data support the use of medications for reducing the severity of core PTSD symptoms and comorbid anxiety and depression, and for significantly improving PTSD symptoms. There was no data to support one class of medication over another, and it was not possible to predict response to medications.

Background: PTSD, by definition, involves prior psychological trauma, and psychotherapy has long been a mainstay of treatment. However, there has been increasing recognition that PTSD is characterized by specific neurobiological dysfunctions, dysfunctions that could conceivably be treated by pharmacotherapy.

Clinical Case/Questions: 1) Is there evidence for the use of medications in PTSD?; 2) If so, are there particular classes of medications more efficacious than others?; 3) Are there clinical or methodological factors that predict response to medications?

Methods: This was a Cochrane Review of all RCTs of PTSD pharmacotherapy (including both placebo controlled and comparative trials, whether published or unpublished) completed prior to the end of 1999. Electronic bibliographic databases (MEDLINE 1966 to 1999, PSYCHLIT, The National PTSD Center Pilots database, Dissertation Abstracts, and The Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register) were searched. Additional RCTs were requested from researchers and from pharmaceutical companies, but conference proceedings were not systematically utilized. RCTs were selected which were of 12 weeks or less duration and had enough data for analysis. Each included study was assessed for quality by using the CCDAN Quality of Research Scale; this scale was completed for each study by two reviewers.

Validity: The present overview did address a specific clinical question, albeit it is a broad one (use of pharmacotherapy in PTSD). This study used rather broad inclusion criteria; no attempt was made to include or exclude studies based on different diagnostic criteria for PTSD, duration and severity of PTSD symptoms, presence of comorbid disorders, or age and gender of subjects. It is easily conceivable that the studies chosen for inclusion varied drastically in the type of patient population studied and perhaps even the form of PTSD (with comorbidities or without). Including all these types of studies might limit the ability to form a strong conclusion. On the other hand, these broad inclusion criteria do allow a conclusion to be applied to a larger patient population. Interestingly, the overview focused on short term trials (less than 12 weeks) and did not look for longer term trials (perhaps including the requirement for short term trials was too stringent). This overview included both published and unpublished data; unpublished data may be of lesser quality and may dilute the strengths of the conclusions. MEDLINE searches were from 1966, and the earlier studies suffered from methodological problems such as low power and imprecise patient outcome measures (often self-report); including these trials may dilute the strengths of the conclusions. It is unlikely that important, relevant studies were missed precisely because the inclusion criteria were so broad. The validity of the included studies was appraised with the CCDAN Quality of Research Scale, but appraisals did not affect the overall data analyses since data were pooled. Assessments of studies were done by two independent raters and then a consensus was reached; it is unclear if these assessments were reproducible within and across raters. It is unclear if the results were similar across the trials.

Results: Fifteen short term RCTs were found, of which 13 were included because they provided post-treatment medication and placebo categorical response rates or dimensional symptom means/standard deviations (enough data to put into an analysis). Based on Clinical Global Impressions scale change item (CGI-C) and Clinical Global Impressions scale severity item (CGI-S), patients who received medication were significantly less likely to be non­responders and had decreased severity of symptoms compared to placebo (RR=0.72, 95% CI=0.64;lower severity by 0.74 units, CI=0.87, 1.12; CAPS-2 score lower by 0.46 SD units, CI=0.20, 0.71). There was no significant difference between types of trials (non-combat trauma vs. combat trauma - CI 0.60, 0.81 and CI 0.66, 0.86 respectively) on CGI-C score and trials that included clinician-rated scales and those that did not (CI 0.66, 0.86 and 0.29, 0.74). There was no significant difference when types of medications were compared: SSRIs (0.75, CI=0.65, 0.88), older non-SSRI antidepressants (0.62, CI=0.45, 0.86), and TCA/MAOI trials (0.48, CI=0.32, 0.72). Core PTSD symptoms were improved with medication more than placebo based on the Impact of Events Scale. The medications were also more effective than placebo for comorbid depression and anxiety. Medications improved quality of life more than placebos (by 0.44 units, CI=0.03, 0.85). Drop out rates for medication vs. placebo were not significantly different (RR=0.85, CI=0.63, 1.14) and drop out rates did not vary by type of medication: SSRI (0.99, CI=0.68, 1.44), non-SSRI (0.70, CI=0.43, 1.14), and TCA/MAOI (0.70, CI=0.32, 1.41)

Comments: This study meets most criteria for validity for a meta-analysis. The study is useful in providing evidence for the use of pharmacotherapy for PTSD. Future studies need to compare pharmacotherapy with psychotherapy, and compare across medications.

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SINGLE SESSION PSYCHOLOGICAL DEBRIEFING FOR MANAGEMENT OF PSYCHOLOGICAL DISTRESS AFTER TRAUMA

Author:
Alyson Kuroski, DO

Bottom Line: At this time, the routine use of single session psychological debriefing given to non selected trauma victims cannot be recommended.

Background: Debriefing has been defined as a psychological treatment intended to reduce the psychological morbidity that arises after exposure to trauma (Hodgkinson & Stewart, cited in Rose, 1997). It involves promoting some form of emotional processing, catharsis, or ventilation by encouraging recollection, ventilation, and reworking of the traumatic event led by an experienced mental health professional. Furthermore, it has been broken down into seven specific portions, by Mitchell, 1983 and Dyregov, 1989, including an introduction, the facts, thoughts and impressions, emotional reactions, normalization, planning for the future, and disengagement. Of note, these stages have been described and quantified differently by various authors. Debriefing has been used in recent years in a myriad of circumstances and has become a compulsory practice for some organizations. The assumption is naturally that debriefing can decrease acute distress and prevent the onset of PTSD that follows traumatic incidents. The data surrounding this assumption is very controversial and, thus, a review of the current literature was completed.

Search Method: The evaluators utilized an electronic searching of MEDLINE, EMBASE, PsychLit, PILOTS, Biosis, Pascal, Occ. Safety and Health, SOCIOFILE, CINAHL, PSYCINFO, PSYNDEX, SIDLE, LILACS, CCTR, CINAHL, NRR, hand search of Journal of Traumatic Stress, and contact with leading researchers.

Clinical Question: Is single session psychological debriefing effective for the management of psychological distress after trauma, specifically assault in regards to this writer's pt, and prevention of PTSD?

Reference: Rose, S; Bisson, J; Wessely, S. Psychological debriefing for preventing PTSD (Cochrane Review). The Cochrane Library, Issue 3, 2002.

Methods: 11 randomized trials were chosen for evaluation that focused on persons recently (one month or less) exposed to a traumatic event, consisted of only a single session, and involved some form of emotional processing/ventilation by encouraging recollection/reworking of the traumatic event accompanied by normalization of emotional reaction to the event. These trials were reviewed and agreed upon for inclusion by the three reviewers individually according to three standard quality assessments. The three quality assessments included the methods described in the Cochrane Collaboration Handbook (A-C levels of evidence), the quality ratings scale devised by Churchill. 1996 (QC) with max of 37 for studies of psychiatric interventions, and the quality ratings scale devised by Kenardy & Carr,1996 (QK) with max of 26 for studies of debriefing. Additionally, the principal continuous measure used in all the modern trials was the Impact of Events Scale (IES). Lastly, for categorical outcomes the Peto method for computing the pooled odds ratio was used.

Results: Single session individual debriefing did not reduce psychological distress nor prevent the onset of PTSD. Those who received the intervention showed no significant short term (3-5 months) decrease in the risk of PTSD (odds ratio 1.22 (95% CI 0.06 to 2.46)). At one year, one trial reported that there was a significantly increased risk of PTSD in those receiving debriefing (odds ratio 2.88 (95% CI 1.11 to 7.53)).

Comments: The study populations are reasonably comparable apart from the three studies involving childbirth/miscarriage and the Bunn,1979 study focusing on relatives of trauma victims. Also, most studies showed an excess of males, reflecting the