Psychiatric Annals

CME Article 

Clinical Considerations at Each Stage of Evaluation and Treatment of Trauma Survivors and PTSD

Kathryn M. Connor, MD; Dan J. Stein, MD

Abstract

Posttraumatic disorder (PTSD) can be a challenging condition to diagnose and treat. Proper recognition often is complicated by the variety of clinical presentations and comorbidities, including depression, suicidality, psychotic features, and substance use problems.

While treatment response is influenced by many factors, some considerations, such as the presence of ongoing trauma, are particularly salient to PTSD. To maximize treatment outcome, clinicians need to be aware of these considerations, both at the time of the initial evaluation of treatment survivors and at each stage of treatment in patients with PTSD. A PTSD treatment algorithm, as discussed elsewhere in this issue, needs to ensure that these factors are considered at each step and managed appropriately.

In this article, we discuss clinical issues relevant to each stage of evaluation and treatment of PTSD. These include suicidality, comorbid diagnoses, insomnia or nightmares, psychosis, substance abuse, treatment nonadherence, ongoing trauma, cultural issues, litigation issues, and psychosocial treatment. A final issue, PTSD concerns in women of childbearing potential, is discussed in the (see page 910). The levels of evidence (LOE) referenced in this article are defined in the text and Table 1 of the article by Davidson et al. (see page 889).

Compared with the general population, trauma survivors and patients with PTSD have exhibited elevated rates of attempted suicide, even among those without depression.1,2 In these populations, it is important that additional risk factors for suicidality be considered, including cluster B personality features or disorder, total number of PTSD symptoms, presence of ongoing trauma, depression, substance use problems, attention-deficit/hyperactivity disorder, and lack of social support.

Patients with suicidal ideation need to be carefully evaluated in terms of potential risk for suicide and, where necessary, treated in a supportive environment where they will be safe from immediate harm and where adequate pharmacotherapeutic and psychosocial treatment can be initiated, along with attempts to build and engage support. While suicidal patients typically are excluded from controlled treatment trials, it would be rational to begin standard first-line antidepressants for PTSD in these patients. Certainly, antidepressant treatment in PTSD has been shown to decrease both PTSD symptoms, as well as comorbid symptoms including depressive symptoms.

Although rare, there is the possibility of early activation or agitation in the first few days after initiating antidepressant treatment, provoking suicidal or aggressive behavior in some cases. Careful clinical monitoring and education can help mitigate these effects.

Patients under evaluation for PTSD often present with other symptoms and comorbid psychiatric or medical diagnoses. Such presentations may complicate recognition of PTSD and alter the treatment approach. At the initial diagnostic evaluation, the clinician should obtain a full psychiatric and medical history with appropriate consideration of referral for physical exam and laboratory tests as indicated clinically. As part of the initial assessment and after each subsequent treatment trial, if the response is unsatisfactory, the clinician should be alert to the potential presence of commonly co-present psychiatric conditions, such as depression and other anxiety disorders. Other features that can affect presentation and that should be considered include confounding insomnia, psychosis, and substance abuse, as well as un-diagnosed medical illnesses (eg, thyroid disease) and ongoing use of anxiety-producing substances such as caffeine.

By definition, PTSD develops after a traumatic experience,3 but such experiences also can play a causal role in a range of other disorders.4 This observation is supported by the high rates of other comorbid disorders in PTSD. For example, in the National Comorbidity Survey (NCS), major depression and alcohol abuse or dependence were the most common comorbid disorders in men with PTSD (48% and 52%, respectively), while major depression and simple phobia were most commonly comorbid…

Posttraumatic disorder (PTSD) can be a challenging condition to diagnose and treat. Proper recognition often is complicated by the variety of clinical presentations and comorbidities, including depression, suicidality, psychotic features, and substance use problems.

While treatment response is influenced by many factors, some considerations, such as the presence of ongoing trauma, are particularly salient to PTSD. To maximize treatment outcome, clinicians need to be aware of these considerations, both at the time of the initial evaluation of treatment survivors and at each stage of treatment in patients with PTSD. A PTSD treatment algorithm, as discussed elsewhere in this issue, needs to ensure that these factors are considered at each step and managed appropriately.

In this article, we discuss clinical issues relevant to each stage of evaluation and treatment of PTSD. These include suicidality, comorbid diagnoses, insomnia or nightmares, psychosis, substance abuse, treatment nonadherence, ongoing trauma, cultural issues, litigation issues, and psychosocial treatment. A final issue, PTSD concerns in women of childbearing potential, is discussed in the (see page 910). The levels of evidence (LOE) referenced in this article are defined in the text and Table 1 of the article by Davidson et al. (see page 889).

Suicidality

Compared with the general population, trauma survivors and patients with PTSD have exhibited elevated rates of attempted suicide, even among those without depression.1,2 In these populations, it is important that additional risk factors for suicidality be considered, including cluster B personality features or disorder, total number of PTSD symptoms, presence of ongoing trauma, depression, substance use problems, attention-deficit/hyperactivity disorder, and lack of social support.

Patients with suicidal ideation need to be carefully evaluated in terms of potential risk for suicide and, where necessary, treated in a supportive environment where they will be safe from immediate harm and where adequate pharmacotherapeutic and psychosocial treatment can be initiated, along with attempts to build and engage support. While suicidal patients typically are excluded from controlled treatment trials, it would be rational to begin standard first-line antidepressants for PTSD in these patients. Certainly, antidepressant treatment in PTSD has been shown to decrease both PTSD symptoms, as well as comorbid symptoms including depressive symptoms.

Although rare, there is the possibility of early activation or agitation in the first few days after initiating antidepressant treatment, provoking suicidal or aggressive behavior in some cases. Careful clinical monitoring and education can help mitigate these effects.

Comorbid Diagnosis

Patients under evaluation for PTSD often present with other symptoms and comorbid psychiatric or medical diagnoses. Such presentations may complicate recognition of PTSD and alter the treatment approach. At the initial diagnostic evaluation, the clinician should obtain a full psychiatric and medical history with appropriate consideration of referral for physical exam and laboratory tests as indicated clinically. As part of the initial assessment and after each subsequent treatment trial, if the response is unsatisfactory, the clinician should be alert to the potential presence of commonly co-present psychiatric conditions, such as depression and other anxiety disorders. Other features that can affect presentation and that should be considered include confounding insomnia, psychosis, and substance abuse, as well as un-diagnosed medical illnesses (eg, thyroid disease) and ongoing use of anxiety-producing substances such as caffeine.

By definition, PTSD develops after a traumatic experience,3 but such experiences also can play a causal role in a range of other disorders.4 This observation is supported by the high rates of other comorbid disorders in PTSD. For example, in the National Comorbidity Survey (NCS), major depression and alcohol abuse or dependence were the most common comorbid disorders in men with PTSD (48% and 52%, respectively), while major depression and simple phobia were most commonly comorbid in women with PTSD (49% and 29%, respectively).5 Similarly, high rates of depression are found in clinical samples of patients with PTSD.6 Patients with PTSD and depression are likely to be sicker, with greater distress and role impairment, and are more likely to report suicidal ideation.7

From the perspective of an algorithmic approach to the pharmacologic management of PTSD, selective serotonin reuptake inhibitors (SSRIs) are considered first-line pharmacotherapy. The SSRIs are thought to be useful whether or not comorbidity with depression and anxiety disorders are present. Certainly, several of the positive SSRI trials in PTSD have included large numbers of subjects with comorbid depression, and secondary analyses have demonstrated the efficacy of medication over placebo irrespective of the presence of comorbidity.

Cognitive-behavioral therapy (CBT) also can be used to treat PTSD with comorbid depression and anxiety disorders, although there is less data in this area (LOE 4). Further, the form of CBT may need to be altered to address the range of presenting symptoms.

In other instances, PTSD with certain comorbidities requires an adjustment in therapeutic approach. For example, in patients with comorbid substance use problems, it may be important initially for the substance use disorder to be the primary target of treatment. In patients with comorbid bipolar disorder, it is important to ensure that a mood stabilizing agent is used before an antidepressant is begun. Thus, a careful evaluation for comorbidity is needed before initiating treatment, and the choice of treatment needs to be formulated with appropriate clinical judgment. There is a need for effectiveness trials to determine the optimal management of PTSD in settings outside typical clinical trials contexts, where there may be increased psychiatric and general medical comorbidity.

Insomnia or Nightmares

Sleep problems in patients with PTSD may represent core symptoms of the disorder or may be a symptom of another underlying condition that may have medical, psychiatric, or behavioral origins. Sleep disruption characterized by insomnia and nightmares, core symptoms of PTSD, may respond to standard first-line interventions. However, disturbed sleep often persists despite treatment with some SSRI agents and, in some cases, may even be exacerbated by these medications.8,9 Under such circumstances, it is important to first assess lifestyle factors, such as concomitant use of stimulating over-the-counter medications or heavy caffeine use, that may be contributing to the sleep disturbance.

The alpha-adrenergic antagonist prazosin can be quite effective in ameliorating nightmares and insomnia in PTSD (LOE 2, 3).10,11 Potential side effects with prazosin include hypotension, syncope, and tachycardia; thus, the patient's predisposition to these effects, especially hypotension, should be considered, and regular blood pressure monitoring should be used. Other pharmacologic options include nefazodone (LOE 2), low-dose sedating tricyclic anti-depressants such as trazodone, doxepin, or amitriptyline (LOE 4), mirtazapine (LOE 4), olanzapine (LOE 4), quetiapine (LOE 4), or zolpidem (LOE 4), all at night.12–17

The role of benzodiazepines to treat sleep disruption in PTSD is less clear. While these medications may be helpful in reducing hyperarousal symptoms during treatment, benzodiazepines do not appear to confer any additional benefit with respect to the course of PTSD (LOE 2, 3).18–20 Also, despite evidence for the effectiveness of the selective gamma-aminobutyric acid reuptake inhibitor (SGRI) tiagabine for improving sleep (LOE 3),21 the recently observed risk of seizures22 warrants exclusion from the first-line recommendations for treating insomnia in patients with PTSD. Among nonpharmacologic treatment options, one approach that has shown promise in decreasing nightmares and in improving overall PTSD symptom severity is imagery rehearsal therapy (LOE 1).23

In the event of continued poor response, a primary sleep disorder, such as the breathing-related sleep disorder obstructive sleep apnea, or other sleep disorder should be considered. If appropriate, based on clinical features, a polysomnogram may be obtained.24 If obstructive sleep apnea is confirmed, then treatment with continuous positive airway pressure is indicated (LOE 4). If the evaluation does not reveal an apparent cause, an alternative medication may be selected from the list above.

Psychosis

Psychotic features are not uncommon in PTSD and may present in as many as 40% of patients with PTSD.25 Commonly reported symptoms include hallucinations, delusions, and paranoid ideation. At the outset of evaluation and treatment, it is essential to determine whether psychotic features are best explained as part of the overall PTSD syndrome or whether they are most consistent with a comorbid primary psychotic disorder or mood disorder with psychotic features. If the former, treatment for PTSD should be initiated with SSRIs, bearing in mind that these patients may not respond adequately to those medications.

Flashbacks, hypervigilance, and dissociation often observed in PTSD can all manifest with psychotic presentation. In such cases, there is some limited evidence that antiadrenergic agents and anticonvulsants may be beneficial (LOE 4). Failure to respond to such agents, however, would suggest augmentation with an atypical antipsychotic. Indeed, persistent fearful, paranoid, and hyper-vigilant symptoms might benefit from atypical antipsychotics. If, on the other hand, PTSD is comorbid with a thought disorder, augmentation with atypical antipsychotics should be considered from the outset of treatment.

Much work in the area of psychotic symptoms presenting with PTSD has focused on augmentation of SSRIs with atypical antipsychotics. To date, evidence is available for augmentation with risperidone (LOE 2), olanzapine (LOE 3), and quetiapine (LOE 3). This evidence base is limited largely to combat veterans,15,19,26–28 with one study in civilians.29 Further, the evidence is inconclusive, in that some drugs have not separated consistently from placebo30 or have done so only on limited symptom dimensions (eg, psychotic symptoms17 or sleep and mood15).

An inadequate response to the first antipsychotic drug could be followed by switching to a different drug. Further nonresponse is an indication for diagnostic re-evaluation. The specific atypical neuroleptic medication should be chosen after considering the patient's risk for side effects, such as weight gain, aggravation of diabetes, metabolic syndrome, hyperlipidemia, or hyperprolactinemia. The newer atypical antipsychotics, aripiprazole and ziprasidone, may have a more favorable side effect profile and could, theoretically, be used in the treatment of PTSD, but no data exist (LOE 4).

Substance Abuse

Current or Recent Substance Abuse or Dependence

Comorbid substance use is common among patients with PTSD.5 Patients with PTSD are also more likely to have impaired stress tolerance, which may put them at risk for substance abuse or dependence or exacerbation of a substance use disorder. In the presence of a substance use disorder, the patient with PTSD is first required to undergo withdrawal from his or her substance(s). The patient must make a commitment to abstain from future use of these substances, although the patient may not succeed in meeting this commitment, and compliance with this commitment must be monitored closely. The PTSD pharmacologic treatment algorithm recommendations (and their associated evidence-base) will not be relevant to patients returning to active substance abuse or dependency.

As a general principle, use of conservative (eg, less toxic agents) and less complicated regimens is advisable whenever possible with such patients. Early treatment with SSRIs may be beneficial in this population, although the largest (LOE 2) trials to date fail to demonstrate greater benefit from sertraline than placebo (LOE 2).31 Comorbid substance abuse and PTSD is a relative contraindication for the treatment with benzodiazepines, except when prescribed in conjunction with a detoxification program from alcohol or sedatives.

For the algorithm's recommendations to apply, the patient should have completed withdrawal from drug(s) of abuse or dependence, as well as from any pharmacotherapy used for withdrawal prophylaxis, and should be abstinent for at least 1 additional week. This time frame appears to be the minimum period after which drug–placebo differences have been demonstrated in treatment trials of anxiety and depressive disorders that persist after, for example, alcohol withdrawal.32,33 Symptoms present after abstinence of less than 1 week may be due in part to the residual effects of the substance. If symptoms appear to be diminishing during the first week of sobriety, and in the absence of these symptoms prior to onset of the substance abuse/dependency or during previous periods of extended sobriety, it is reasonable to wait at least another week before initiating pharmacotherapy to see if the symptoms resolve spontaneously after further abstinence.

Some substances may have a prolonged withdrawal period, and the residual effects of their presence may affect the benefit of subsequent medications. For example, effects with the opioid methadone, which has a half-life of approximately 48 hours and is an inhibitor of cytochrome P450 2D6, could persist beyond a week.

A common clinical presentation not specifically addressed in this algorithm is the patient with PTSD who also uses drugs of abuse but does not meet full criteria from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV),34 for substance abuse or dependence. It is not known if the sequence of treatments for these “recreational” users should be any different from the standard approach to be effective. To date, these frequently encountered patients have received little research attention.

History of Substance Abuse

PTSD patients who are not actively abusing or dependent on substances but who have a history of such abuse/dependence may require relapse prevention treatment. For example, the patient may have recently been detoxified, be under unusual stress, or be experiencing strong cravings for the substance and may therefore be at high risk of relapse. This suggests that management of the problem would have a priority at least as high as, if not higher than, treating PTSD.

For patients with alcohol use disorders, evidence-supported pharmacotherapeutic options include naltrexone, acamprosate, and topiramate (all LOE 1 for the index disorder).35–38 Topiramate also has been reported to be helpful for PTSD (LOE 4)39 and with more research may emerge as a particularly good choice for the patient with comorbid alcohol cravings and PTSD. For cocaine dependency, disulfiram may be of value for preventing relapse (PTSD, LOE 4; cocaine, LOE 2).40

Pharmacotherapy options for substance abuse/dependence are most effective when administered in conjunction with ongoing, intensive, structured psychotherapy with a strong focus on treatment compliance and relapse prevention.36 Indeed, without this element, no medication may be better than placebo.

If the patient has been assessed for these options and considered appropriate, the user may then follow the standard PTSD treatment algorithm starting with Node 1 recommendations (Davidson et al., see page 887). At any stage, these options should be reconsidered if new information suggests the substance problems are at high risk for re-emerging. A review of the application of pharmacologic treatment algorithms for anxiety disorders in patients with substance abuse or dependence has been published previously.41

Treatment Nonadherence

A discussion about the expected effects of medication and how to deal with problems that arise is essential when starting any new medication. Nonadherence rates with antidepressants in depression may be as high as 50% at 3 months.42,43 Shemesh and colleagues44–46 have demonstrated that medical patients with PTSD (in adults secondary to myocardial infarction and in children secondary to liver transplantation) have high rates of medication nonadherence. In the presence of nonresponse, it is important to consider nonadherence as a cause.

Lin et al.47,48 have suggested a number of strategies to help improve treatment adherence in depression, and these strategies may also be helpful in PTSD. Of particular note were several educational messages to patients, listed in the Sidebar (see page 905). It is also important to consider issues unique to PTSD; a patient may be reluctant to be in treatment, perhaps blaming his or her plight on the unwelcome trauma. Having to take medication is viewed by some patients as a re-traumatization, and in such cases, it may be necessary to address this issue in psychotherapy.

Sidebar.

Patient Education Recommendations to Help Improve Treatment Adherence

  1. Take the medication daily.

  2. Remember that antidepressants must be taken for 4 to 6 weeks for a noticeable effect.

  3. Continue to take medicine even if you are feeling better.

  4. Do not stop taking an antidepressant without checking with your physician.

  5. Read the instructions regarding what to do to resolve questions concerning medication.

  6. Schedule pleasant activities.

Patient Education Recommendations to Help Improve Treatment Adherence

Ongoing Trauma

It is widely believed that full recovery is unlikely in the setting of ongoing trauma, such as with continued exposure to abusive violence in a relationship (LOE 4). This opinion is an extrapolation from the CBT literature. Intervention to provide an environment safe from ongoing trauma is essential. It is not known, however, whether medication can at least ameliorate PTSD symptoms in patients who remain in threatening or dangerous environments. In addition to ongoing trauma, it is also important to consider more subtle disadvantageous social circumstances that may contribute to worse symptoms and treatment outcome (eg, loss of social supports) and to try address them.

Cultural Issues

It has been suggested that PTSD is characterized not by a normal stress response but rather by pathological sensitization of particular psychobiological systems.49 It is not surprising, therefore, that a good deal of evidence demonstrates that PTSD symptoms are similar in different historical eras and in different cultures.50 A recent examination of the effects of terrorist bombings in Ibaden, Nigeria, and Oklahoma City, Oklahoma, found similar increases in rates of PTSD 6 to 10 months after the disasters and similar rates of symptoms within each PTSD symptom cluster.51 At the same time, it is important to acknowledge that types of trauma differ across cultures and that PTSD may be experienced and expressed differently in different societies.52

Friedman and Marsella,50 for example, suggest that, while the re-experiencing (cluster B) and hyperarousal (cluster D) symptoms of PTSD are universal, the avoidant and numbing symptoms (cluster C) are more likely experienced in those ethnocultural settings where avoiding and numbing behaviors are common expressions of distress. There also may be trans-cultural variation in extent of dissociation and somatization after trauma.53 Cultural and social factors may be important determinants of vulnerability to PTSD by shaping concepts of what constitutes a trauma and by affecting known vulnerability factors such as early childhood experiences, comorbidity (eg alcohol abuse), and social resources for responding to trauma. Once again, however, many of these questions remain open for future rigorous empirical research.50

Nevertheless, a strong theoretical argument can be provided to the effect that particular cultural rituals, performed after exposure to trauma, do play a role in preventing PTSD.54 Conversely, it is possible to speculate that repression of trauma narratives in certain cultures exacerbates posttraumatic suffering. An interesting experiment at a national level recently took place in South Africa, where a Truth and Reconciliation Commission encouraged the public acknowledgment of past gross human rights violations.55 Although rates of PTSD were no lower in those who gave testimony, there was a relationship between increased psychopathology and decreased forgiveness. Other work has indicated that there may be a therapeutic effect of bearing witness to past human rights violations.56

Given that the psychopathology of PTSD frequently involves not only discrete symptoms but also a broader questioning of the self and of identity, understanding the patient's sociocultural background is particularly important. Several authors have emphasized that inadequate appreciation of the sociocultural context of trauma and responses to trauma may impede the therapeutic process. On the other hand, a comprehensive and sensitive assessment of this context may allow appropriate individual and community interventions that promote symptomatic improvement as well as broader healing.

Several symptom rating scales have been used in multiple social and cultural contexts. These include the clinician-rated Clinician Administered PTSD Scale (CAPS)57 and Composite International Diagnostic Interview (CIDI)5 and the patient-rated Harvard Trauma Questionnaire (HTQ).58

Biological differences that can affect drug metabolism also exist across ethnic groups. For example, there is increasing understanding of the inter-individual differences that affect maximum tolerated doses of medication. Variants of cytochrome P450 isoenzymes may affect the metabolism of antidepressants, antipsychotics, and benzodiazepines. Particular variants may be more common in certain ethnic groups.59 Generalizing from pharmacokinetic research, Lin et al suggest, for example, that Asians may respond to lower doses of psychotropic medication than Caucasians.60

In addition, financial and formulary constraints often limit the use of a number of medications suggested in this algorithm, but in ways that vary from one country to another. It should be noted, however, that several SSRIs are now available in generic form.

Litigation Issues

If a patient is involved in legal action related to a traumatic event, it is quite possible that symptoms will be exacerbated on occasions when the traumatic event has to be recalled, particularly under adversarial circumstances. If the individual believes that compensation is essential to recovery, this may also influence the extent of response to pharmacotherapy. However, no empirical data exist on this matter (LOE 4).

Psychosocial Treatment

In developing a treatment plan for patients with PTSD, the first choice to be made is whether to offer medication, psychosocial treatment, or both. Patient preference and the availability of qualified therapists will influence the modality of treatments selected. Both medication and psychotherapeutic treatment have demonstrated efficacy in PTSD (LOE 1). Psychosocial treatment, if not used initially, can be added to or may replace pharmacotherapy in those who are unresponsive or unable to tolerate medications. Empirical data to support the augmentation of medication with psychosocial treatments are sparse,61 although this is a widely used approach in clinical practice.

CBT, prolonged exposure, and other psychosocial treatment approaches, such as eye movement desensitization and reprocessing, are of proven efficacy in PTSD (LOE 1).62 These modalities are credible first (or subsequent) choices, provided that a qualified therapist is available and the patient is willing to make the necessary efforts (eg, willing to do homework assignments and potentially experience more distress). One nonpharmacologic approach that has shown promise in decreasing nightmares and in improving overall PTSD symptom severity is imagery rehearsal therapy (LOE 1).22

Summary

When employing a pharmacologic treatment algorithm for the treatment of PTSD, it is important to continuously assess a range of different factors that may influence response to interventions and to tailor the management plan accordingly. Fortunately, there is a significant body of data to suggest that antidepressants, a first-line treatment choice in PTSD, also are useful for comorbid disorders, in particular depression. However, an important reason for developing treatment algorithms is to pinpoint important gaps in the literature, and there are several unknowns in formulating an approach to PTSD patients with different kinds of presentation and comorbidity. Effectiveness trials in “real-life” settings may eventually be useful in addressing some of these. In the interim, algorithms will need to be applied with substantial clinical judgment.

References

  1. Davidson JRT, Hughes DC, Blazer DG, George LK. Post-traumatic stress disorder in the community: an epidemiological study. Psychol Med. 1991;21(3):713–721. doi:10.1017/S0033291700022352 [CrossRef]1946860
  2. Horowitz MJ, Wilner N. Field studies on the impact of life events. In: Horowitz MJ, Northvale NJ, Aronson J, eds. Stress Response Syndromes. 2nd ed. Northvale, NJ: Aronson; 1986:43–68.
  3. Ursano RJ, Bell C, Eth S, et al. Work Group on ASD and PTSD, Steering Committee on Practice Guidelines. Practice Guidelines for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder. Am J Psychiatry. 2004:161(11 Suppl)1–31.
  4. Kendler K, Karkowski LM, Prescott CA. Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry. 1999;156(6):837–841. doi:10.1176/ajp.156.6.837 [CrossRef]10360120
  5. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52(12):1048–1060. doi:10.1001/archpsyc.1995.03950240066012 [CrossRef]7492257
  6. Shalev AY. Measuring outcome in post-traumatic stress disorder. J Clin Psychiatry. 2000;61(Suppl 5):33–39.
  7. Brady KT, Sonne SC, Roberts JM. Sertraline treatment of comorbid posttraumatic stress disorder and alcohol dependence. J Clin Psychiatry. 1995;56(11):502–505.7592501
  8. Meltzer-Brody S, Connor KM, Churchill E, Davidson JR. Symptom-specific effects of fluoxetine in posttraumatic stress disorder. International Clin Psychopharmacol. 2000;15(4):227–231. doi:10.1097/00004850-200015040-00006 [CrossRef]
  9. Davidson JR, Landerman LR, Farfel GM, Clary CM. Characterizing the effects of sertraline in post-traumatic stress disorder. Psychol Med. 2002;32(4):661–670. doi:10.1017/S0033291702005469 [CrossRef]12102380
  10. Raskind MA, Thompson C, Petrie EC, et al. Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder. J Clin Psychiatry. 2002;63(7):565–568. doi:10.4088/JCP.v63n0705 [CrossRef]12143911
  11. Raskind MA, Peskind ER, Kanter ED, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003;160(2):371–373. doi:10.1176/appi.ajp.160.2.371 [CrossRef]12562588
  12. Davidson JR, Kudler H, Smith RD, et al. Treatment of posttraumatic stress disorder with amitriptyline and placebo. Arch Gen Psychiatry. 1990;47(3):259–266. doi:10.1001/archpsyc.1990.01810150059010 [CrossRef]2407208
  13. Hertzberg MA, Feldman ME, Beckham JC, Davidson JR. Trial of trazodone for post-traumatic stress disorder using a multiple baseline group design. J Clin Psychopharmacol. 1996;16(4):294–298. doi:10.1097/00004714-199608000-00004 [CrossRef]8835704
  14. Dieperink ME, Drogemuller L. Zolpidem for insomnia related to PTSD. Psychiatr Serv. 1999;50(3):421. doi:10.1176/ps.50.3.421 [CrossRef]10096658
  15. Stein MB, Kline NA, Matloff JL. Adjunctive olanzapine for SSRI-resistant combat-related PTSD: a double-blind, placebo-controlled study. Am J Psychiatry. 2002;159(10): 1777–1779. doi:10.1176/appi.ajp.159.10.1777 [CrossRef]12359687
  16. Taylor F, Raskind MA. The alpha-1 adrenergic antagonist prazosin improves sleep and nightmares in civilian trauma posttraumatic stress disorder. J Clin Psychopharmacol, 2002;22(1):82–85. doi:10.1097/00004714-200202000-00013 [CrossRef]11799347
  17. Hamner MB, Deitsch SC, Brodrick PS, Ulmer HG, Lorberbaum JP. Quetiapine treatment in patients with posttraumatic stress disorder: an open trial of adjunctive therapy. J Clin Psychopharmacol. 2003;23(1):15–20. doi:10.1097/00004714-200302000-00003 [CrossRef]12544370
  18. Braun P, Greenberg D, Dasberg H, Lerer B. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. J Clin Psychiatry. 1990;51(6):236–238.2189869
  19. Gelpin E, Bonne O, Peri T, Brandes D, Shalev AY. Treatment of recent trauma survivors with benzodiazepines: a prospective study. J Clin Psychiatry. 1996;57(9):390–394.9746445
  20. Mellman TA, Bustamante V, David D, Fins AI. Hypnotic medication in the aftermath of trauma. J Clin Psychiatry. 2002;63(12): 1183–1184. doi:10.4088/JCP.v63n1214h [CrossRef]
  21. Taylor FB. Tiagabine for posttraumatic stress disorder: a case series of 7 women. J Clin Psychiatry. 2003;64(12):1421–1425. doi:10.4088/JCP.v64n1204 [CrossRef]
  22. US Food and Drug Administration Public Health Advisory: Seizures in Patients Without Epilepsy Being Treated With Gabitril (tiagabine). February18, 2005. Available at: http://www.fda.gov/cder/drug/advisory/gabitril.htm. Accessed October 25, 2005.
  23. Krakow B, Hollifield M, Johnston K, et al. Imagery rehearsal therapy for chronic nightmares in sexual assault survivors with post-traumatic stress disorder: a randomized controlled trial. JAMA. 2001;286(5):537–545. doi:10.1001/jama.286.5.537 [CrossRef]11476655
  24. Krakow B, Melendrez D, Petersen B, et al. Complex insomnia: insomnia and sleep-disordered breathing in a consecutive series of crime victims with nightmares and PTSD. Biol Psychiatry. 2001;49(11):948–953. doi:10.1016/S0006-3223(00)01087-8 [CrossRef]11377413
  25. Hamner MB, Faldowski RA, Ulmer HG, Frueh BC, Huber MG, Arana GW. Adjunctive risperidone treatment in posttraumatic stress disorder: a preliminary controlled trial of effects on comorbid psychotic symptoms. Int Clin Psychopharmacol. 2003;18(1):1–8.
  26. Hamner MB, Frueh BC, Ulmer HG, Arana GW. Psychotic features and illness severity in combat veterans with chronic posttraumatic stress disorder. Biol Psychiatry. 1999; 45(7):846–852. doi:10.1016/S0006-3223(98)00301-1 [CrossRef]10202572
  27. Monnelly EP, Ciraulo DA, Knapp C, Keane T. Low-dose risperidone as adjunctive therapy for irritable aggression in posttraumatic stress disorder. J Clin Psychopharmacol. 2003; 23(2):193–196. doi:10.1097/00004714-200304000-00012 [CrossRef]12640221
  28. Bartzokis G, Lu PH, Turner J, Mintz J, Saunders CS. Adjunctive risperidone in the treatment of chronic combat-related post-traumatic stress disorder. Biol Psychiatry. 2005;57(5):474–479. doi:10.1016/j.biopsych.2004.11.039 [CrossRef]15737661
  29. Reich DB, Winternitz S, Hennen J, Watts T, Stanculescu C. A preliminary study of risperidone in the treatment of posttraumatic stress disorder related to childhood abuse in women. J Clin Psychiatry. 2004;65(12):1601–1606. doi:10.4088/JCP.v65n1204 [CrossRef]
  30. Butterfield MI, Becker ME, Connor KM, Sutherland S, Churchill LE, Davidson JR. Olanzapine in the treatment of post-traumatic stress disorder: a pilot study. Int Clin Psychopharmacol. 2001;16(4):197–203. doi:10.1097/00004850-200107000-00003 [CrossRef]11459333
  31. Brady KT, Sonne S, Anton RF, Randall CL, Back SE, Simpson K. Sertraline in the treatment of co-occurring alcohol dependence and posttraumatic stress disorder. Alcohol Clin Exp Res. 2005;29(3):395–401. doi:10.1097/01.ALC.0000156129.98265.57 [CrossRef]15770115
  32. Kranzler HR, Burleson JA, Del Boca FK, et al. Buspirone treatment of anxious alcoholics: a placebo controlled trial. Arch Gen Psychiatry. 1994;51(9):720–731. doi:10.1001/archpsyc.1994.03950090052008 [CrossRef]8080349
  33. Mason BJ, Kocsis JH, Ritvo EC, Cutler RB. A double-blind, placebo-controlled trial of desipramine for primary alcohol dependence, stratified on the presence or absence of major depression. JAMA. 1996;275(10):761–767. doi:10.1001/jama.1996.03530340025025 [CrossRef]8598592
  34. American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders, 4th edition. Washington, DC: American Psychiatric Press. 1994.
  35. Srisurapanont M, Jarusuraisin N. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2005;(1):CD001867.15674887
  36. O'Malley SS. Integration of opioid antagonists and psychosocial therapy in the treatment of narcotic and alcohol dependence. J Clin Psychiatry. 1995;56(Suppl 7):30–38.7673103
  37. Johnson BA, Ait-Daoud N, Akhtar FZ, Ma JZ. Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals. Arch Gen Psychiatry. 2004;61(9):905–912. doi:10.1001/archpsyc.61.9.905 [CrossRef]15351769
  38. Verheul R, Lehert P, Geerlings PJ, Koeter MW, van den Brink W. Predictors of acamprosate efficacy: results from a pooled analysis of seven European trials including 1485 alcohol-dependent patients. Psychopharmacology (Berl). 2005;178(2–3):167–73. doi:10.1007/s00213-004-1991-7 [CrossRef]
  39. Berlant J, van Kammen DP. Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report. J Clin Psychiatry. 2002;63(1):15–20. doi:10.4088/JCP.v63n0104 [CrossRef]11838620
  40. Carroll KM, Fenton LR, Ball SA, et al. Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients. Arch Gen Psychiatry. 2004;61(3):264–272. doi:10.1001/archpsyc.61.3.264 [CrossRef]14993114
  41. Osser DN, Renner JA Jr, Bayog R. Algorithms for the pharmacotherapy of anxiety disorders in patients with chemical abuse and dependence. Psychiatr Ann. 1999;29(5):285–301. doi:10.3928/0048-5713-19990501-10 [CrossRef]
  42. Lin EH, Von Korff M, Katon W, et al. The role of the primary care physician in patients' adherence to antidepressant therapy. Med Care. 1995;33(1):67–74. doi:10.1097/00005650-199501000-00006 [CrossRef]7823648
  43. Lin EH, von Korff M, Ludman EJ, et al. Enhancing adherence to prevent depression relapse in primary care. Gen Hosp Psychiatry. 2003;25(5):303–310. doi:10.1016/S0163-8343(03)00074-4 [CrossRef]12972220
  44. Shemesh E, Lurie S, Stuber ML, et al. A pilot study of posttraumatic stress and non-adherence in pediatric liver transplant recipients. Pediatrics. 2000;105(2):E29. doi:10.1542/peds.105.2.e29 [CrossRef]10654989
  45. Shemesh E, Rudnick A, Kaluski E, et al. A prospective study of posttraumatic stress symptoms and non-adherence in survivors of a myocardial infarction (MI). Gen Hosp Psychiatry. 2001;23(4):215–222. doi:10.1016/S0163-8343(01)00150-5 [CrossRef]11543848
  46. Shemesh E, Yehuda R, Milo O, et al. Posttraumatic stress non-adherence, and adverse outcome in survivors of a myocardial infarction. Psychosom Med. 2004;66(4):521–526. doi:10.1097/01.psy.0000126199.05189.86 [CrossRef]15272097
  47. Lin EH, von Korff M, Ludman EJ, et al. Enhancing adherence to prevent depression relapse in primary care. Gen Hosp Psychiatry. 2003;25(5):303–310. doi:10.1016/S0163-8343(03)00074-4 [CrossRef]12972220
  48. Lin EH, von Korff M, Katon WJ, et al. The role of the primary care physician in patients' adherence to antidepressant therapy. Med Care. 1995;33(1):67–74. doi:10.1097/00005650-199501000-00006 [CrossRef]7823648
  49. Yehuda R, McFarlane AC. Conflict between current knowledge about posttraumatic stress disorder and its original conceptual basis. Am J Psychiatry. 1995;152(12):1705–1713. doi:10.1176/ajp.152.12.1705 [CrossRef]8526234
  50. Friedman MJ, Marsella AJ. Posttraumatic stress disorder : An overview of the concept. In: Marsella AJ, Friedman MJ, Gerrity ET, Scurfield RM (Eds). Ethnocultural Aspects of Posttraumatic Stress Disorder : Issues, Research and Clinical Applications. Washington, DC: American Psychological Association. 1996 :11–32. doi:10.1037/10555-001 [CrossRef]
  51. North CS, Pfefferbaum B, Narayanan P, et al. Comparison of post-disaster psychiatric disorders after terrorist bombings in Nairobi and Oklahoma City. Br J Psychiatry. Jun2005;186:487–493. doi:10.1192/bjp.186.6.487 [CrossRef]15928359
  52. Njenga FG, Nicholls PJ, Nyamai C, Kigamwa P, Davidson JR. Post-traumatic stress after terrorist attack: psychological reactions following the US embassy bombing in Nairobi: Naturalistic study. Br J Psychiatry. Oct2004;185:328–333. doi:10.1192/bjp.185.4.328 [CrossRef]15458993
  53. Stamm BH, Friedman MJ. Cultural diversity in the appraisal and expressions of trauma. In: Shalev AY, Yehuda R, McFarlane AC (Eds). International Handbook of Human Response to Trauma. New York, NY: Kluwer Academic/Plenum Publishers. 1999;69–85.
  54. Shay J. Odysseus in America: Combat Trauma and the Trials of Homecoming. New York, NY: Scribner. 2002.
  55. Stein DJ. Psychiatric aspects of the Truth and Reconciliation Commission in South Africa. Br J Psychiatry. Dec1998;173:455–457. doi:10.1192/bjp.173.6.455 [CrossRef]
  56. Weine SM, Kulenovic AD, Pavkovic I, Gibbons R. Testimony psychotherapy in Bosnian refugees: a pilot study. Am J Psychiatry. 1998;155(12):1720–1726. doi:10.1176/ajp.155.12.1720 [CrossRef]9842782
  57. Weathers FW, Keane TM, Davidson JR. Clinician-administered PTSD scale: a review of the first ten years of research. Depress Anxiety. 2001;13(3):132–156. doi:10.1002/da.1029 [CrossRef]11387733
  58. Mollica RF, Caspi-Yavin Y, Bollini P, Truong T, Tor S, Lavelle J. The Harvard Trauma Questionnaire. Validating a cross-cultural instrument for measuring torture, trauma, and posttraumatic stress disorder in Indochinese refugees. J Nerv Ment Dis. 1992;180(2): 111–116. doi:10.1097/00005053-199202000-00008 [CrossRef]1737972
  59. Nasrallah HA. Avoiding side effects in ethnically diverse patients. CNS Spectr. 2005; 10(3 Suppl 2):21–29. doi:10.1017/S1092852900026572 [CrossRef]
  60. Lin K-M, Poland RE, Anderson D, Lesser IM. Ethnopsychopharmacology and the treatment of PTSD. In: Marsella AJ, Friedman MJ, Gerrity ET, Scarfield RM, eds. Ethnocultural Aspects of Posttraumatic Stress Disorder: Issues, Research and Clinical Applications. Washington, DC: American Psychological Association; 1996;505–526. doi:10.1037/10555-020 [CrossRef]
  61. Rothbaum BO, Foa EB, Davidson JRT, Cahill SP, Compton J, Connor KM, Astin M, Berkebile N. Augmentation of sertraline with prolonged exposure in PTSD. Presented at: Annual Meeting of the American Psychiatric Association. ; May 1–6, 2004. , New York, NY. .
  62. Foa EB, Keane T, Friedman M. Effective Treatments for PTSD. New York, NY: The Guilford Press. 2000.
  63. Czarnocka J, Slade P. Prevalence and predictors of post-traumatic stress symptoms following childbirth. Br J Clin Psychol. 2000;39(Pt 1):35–51. doi:10.1348/014466500163095 [CrossRef]10789027
  64. Ayers S, Pickering AD. Do women get post-traumatic stress disorder as a result of childbirth? A prospective study of incidence. Birth. 2001;28(2):111–118. doi:10.1046/j.1523-536X.2001.00111.x [CrossRef]11380382
  65. Cohen MM, Ansara D, Schei B, Stuckless N, Stewart DE. Posttraumatic stress disorder after pregnancy, labor, and delivery. J Womens Health (Larchmt). 2004;13(3):315–324. doi:10.1089/154099904323016473 [CrossRef]
  66. Loveland Cook CA, Flick LH, Homan SM, Campbell C, McSweeney M, Gallagher ME. Posttraumatic stress disorder in pregnancy: prevalence, risk factors, and treatment. Obstet Gynecol. 2004;103(4):710–717. doi:10.1097/01.AOG.0000119222.40241.fb [CrossRef]15051563
Addendum. PTSD in Pregnancy and the Postpartum Period

Zachary N. Stowe, MD; and D. Jeffrey Newport, MD, MS, MDiv

The prevalence and course of PTSD during pregnancy and the postpartum period has received sparse attention. The majority of reports have documented traumatic obstetrical experiences (eg, labor, delivery, miscarriage, fetal demise, stillbirth) as precipitants of traumarelated symptomatology.

An initial study assessing the incidence of PTSD following “normal” childbirth found that 3% had clinically significant symptoms in all dimensions of PTSD.63 Similarly, a second study excluding women with pre-existing symptoms found that 2.8% fulfilled diagnostic criteria for PTSD at 6 weeks postpartum, decreasing to 1.5% by 6 months postpartum.64 Whether these percentages represent an increase in PTSD or simply the incidence of new onset PTSD in a cohort of women of childbearing age is obscure. Notably, one group found that stress-related symptoms in the postpartum period were associated with the occurrence of two or more pregnancy complications and depression during pregnancy.65

More recent investigations have sought to determine the effects of severe stressful life events on pregnant women (eg, those living in metropolitan New York, NY, during the 9/11 attacks). A recent prospective study found that 7.7% of pregnant women met diagnostic criteria for PTSD.66 The majority of these subjects had comorbid mood disorders or other anxiety disorders. It is remarkable that only 12.3% of the pregnant women with PTSD had sought treatment in the preceding 12 months.

The course of pre-existing PTSD during pregnancy remains an enigma. However, given the high rate of comorbidity, prenatal alterations in sleep architecture, and the neuroendocrine/psychosocial stress of pregnancy and childbirth, there is no reason to anticipate improvement of PTSD symptoms over the course of pregnancy and the postpartum period. Furthermore, depending on the obstetrical course and occurrence of complications, there appears to be an increase in new cases of PTSD in postpartum women.

The interface of these limited data with the available reproductive safety data on psychotropic medications and the proposed PTSD treatment algorithm, while empirical, provides a conservative modification for perinatal PTSD management that reduces fetal/neonatal risk. These recommendations and their justification include:

  1. In women of reproductive years, document method of birth control before initiating treatment.

  2. During pregnancy and lactation, consider psychosocial treatments as first intervention.

  3. When pharmacotherapy is indicated for pregnant or breastfeeding women, use medications with published reproductive safety data (ie, fluoxetine, sertraline, paroxetine, citalopram).

  4. Maximize dose of monotherapy prior to any medication switch or adjunctive pharmacotherapy.

  5. If the treatment response is inadequate and adjunctive pharmacotherapy is indicated, some general rules should govern use in pregnant or breastfeeding women:

    • Valproate, monoamine oxidase inhibitors, and adrenergic agents should be avoided.
    • Typical antipsychotic agents have more reproductive safety data than atypical agents, although the use of anticholinergic agents to manage extrapyramidal symptoms should be avoided.
    • If benzodiazepines are indicated, clonazepam has considerable reproductive safety data, and alprazolam does not require hepatic metabolism.
  6. If pharmacotherapy has already been used during pregnancy, do not decrease or switch medications for breast-feeding.

  7. All women who experience obstetrical complications, traumatic delivery, or fetal/neonatal loss should be evaluated for symptoms of PTSD.

  8. The method of birth control should be documented in breastfeeding women.

Sidebar.

Patient Education Recommendations to Help Improve Treatment Adherence

  1. Take the medication daily.

  2. Remember that antidepressants must be taken for 4 to 6 weeks for a noticeable effect.

  3. Continue to take medicine even if you are feeling better.

  4. Do not stop taking an antidepressant without checking with your physician.

  5. Read the instructions regarding what to do to resolve questions concerning medication.

  6. Schedule pleasant activities.

Patient Education Recommendations to Help Improve Treatment Adherence

Educational Objectives

  1. List the important clinical issues to be considered at each stage of evaluation and treatment in trauma survivors and patients with posttraumatic stress disorder (PTSD).

  2. Discuss the evidence-based pharmacologic treatment options in the setting of comorbid psychiatric disorders in PTSD.

  3. Describe when to implement pharmacologic and/or psychosocial interventions based on specific clinical considerations in patients with PTSD.

Authors

Dr. Connor is research director, Anxiety and Traumatic Stress Program, Duke University School of Medicine, Durham, NC. Dr. Stein is chairman, Department of Psychiatry, Cape Town University School of Medicine, Cape Town, South Africa.

Address reprint requests to: Kathryn M. Connor, MD, Duke University Medical Center, DUMC Box 3812, Durham, NC 27710; or e-mail conno004@mc.duke.edu.

Dr. Connor receives grant/research support from Eli Lilly, Forest, and GlaxoSmithKline; serves on the Speakers' Bureau for Ortho-McNeil, Pfizer, Wyeth, Cephalon, Predix, and Jazz; serves as a consultant to Ortho-McNeil, Pfizer, Schwarz Pharma, King, Cephalon, Predix, and Jazz; and receives other financial/material support from Schwabe, Nutrition 21, Cephalon, Nordic, Solvay, and Allergan. Dr. Stein receives grant/research support from and/or serves as a consultant to AstraZeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, and Wyeth.

10.3928/00485713-20051101-05

Sign up to receive

Journal E-contents