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Evidence-Based Reviews

How to treat PTSD in patients with comorbid mood disorders

Antidepressants may trigger hypomania in patients with bipolar spectrum disorders

Vol. 9, No. 4 / April 2010

Major depressive disorder (MDD) and bipolar spectrum disorders are associated with some symptoms of—and fully defined—posttraumatic stress disorder (PTSD). Many traumatic experiences can lead to this comorbidity, the most common being exposure to or witnessing combat for men and rape and sexual molestation for women.1

Trauma has major prognostic and treatment implications for affectively ill patients, including those whose symptoms do not meet PTSD’s full diagnostic criteria. This article aims to help clinicians by:

  • presenting evidence characterizing the overlap between affective disorders and PTSD
  • reviewing evidence that the bipolar spectrum may be broader than generally thought, an insight that affects PTSD treatment
  • making a case for routine PTSD screening for all patients with affective illnesses
  • recommending PTSD treatments tailored to the patient’s comorbid affective disorder.

Overlap of trauma and affective illness

PTSD is remarkably comorbid with mood disorders. Americans with MDD and bipolar disorder (BPD) are 7 and 9.4 times, respectively, more likely to meet criteria for PTSD than persons in the general population, according to odds ratios Kessler et al2 calculated from the National Comorbidity Survey database.

I have never seen a patient with PTSD who did not also meet criteria for an affective disorder. The concurrence of PTSD and MDD is not the product of overlapping diagnostic criteria. Rather, evidence indicates these are distinct diagnostic entities.3 A review of diagnostic criteria for PTSD and hypomania/mania leads to the same conclusion.

Bipolar spectrum disorders

DSM-IV-TR assumes that mood disorders fall neatly into boxes. Other data (Table 1)48 indicate that these disorders fall along a continuum or—more conservatively—that the scope of bipolarity is much wider than DSM-IV-TR recognizes. This is a controversial topic, and the individual clinician’s position could impact how one manages PTSD patients.

Table 1

Evidence of bipolar spectrum features in major depressive episodes




Akiskal and Mallya, 19874

200 community mental health clinic patients diagnosed as having MDD

50% could be classified as having a bipolar disorder

Benazzi, 19975

203 consecutively presenting patients with depression

45% met criteria for bipolar II disorder

Akiskal and Benazzi, 20056

563 consecutive patients presenting with a DSM-IV-diagnosed MDE

58% showed features of bipolar II disorder

Akiskal et al, 20067

493 patients in a French national study presenting with MDE

65% were determined to fall along the ‘bipolar spectrum’

Rabakowski et al, 20058

880 Polish outpatients presenting with MDE

40% met criteria for bipolar disorder

MDD: major depressive disorder; MDE: major depressive episode

In this article, I include bipolar I disorder, bipolar II disorder, and mixed depression within the “bipolar spectrum disorders.” If one accepts this—and I do—it follows that 50% to 70% of all major depressive episodes (MDEs) are bipolar in nature.49 Depending on your practice setting, you may see a higher or lower base rate of bipolar spectrum disorders.

Mixed depression is not recognized in DSM-IV-TR, and the purpose of this article is not to defend its inclusion as a bipolar spectrum phenomenon. A proposed definition of mixed depression9 requires the presence of an MDE contaminated by ≥3 features of hypomania or mania, without euphoria or inflated self-esteem/grandiosity (Table 2).10

Some experts believe episodes of hypomania and mania frequently occur in the illness course of persons with mixed depression; indeed, mixed depression is a predictor of a bipolar course. It is observed in outpatient9 and inpatient settings.11 Common forms of mixed depression feature combinations of irritability, psychomotor agitation (mild to severe), increased talkativeness (which may fall short of frank pressured speech), racing or “crowded” thoughts (or “mental overactivity”), and distractibility. Other than increased self-esteem/grandiosity, any symptoms within DSM-IV-TR criterion B for a hypomanic or manic episode may be seen in mixed depression. Psychosis is an exclusion criterion for mixed depression.

Mixed depression responds poorly to antidepressant monotherapy. Validation studies suggest that mixed depression is a bipolar variant, as determined by its capacity to predict a bipolar course and its association with a family history of bipolar disorder and age of onset.9

Table 2

Diagnostic characteristics of a hypomanic episode, DSM-IV-TR criteria A and B

A. A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual nondepressed mood.

B. During the period of mood disturbance, 3 or more of the following symptoms have persisted (4 if the mood is only irritable) and have been present to a significant degree:
  1) inflated self-esteem or grandiosity
  2) decreased need for sleep (eg, feels rested after only 3 hours of sleep)
  3) more talkative than usual or pressure to keep talking
  4) flight of ideas or subjective experience that thoughts are racing
  5) distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli)
  6) increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
  7) excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, the person engages in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

Source: Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000

PTSD risk in affective illness

An adolescent sample. A preliminary cross-sectional study conducted by our group indicates that adolescents with affective disorders may have a much higher risk of developing PTSD than psychiatric comparison subjects.12 We used modules from the Structured Clinical Interview for DSM-IV (SCID) to screen for intra-episode psychopathology (as opposed to lifetime prevalence of disorders) in 79 adolescents with MDD, 34 with BPD as defined in the DSM-IV-TR, and 26 with neither affective disorder (psychiatric controls). We found:

  • 38.2% of subjects with BPD met criteria for PTSD, compared with 13.9% of those with MDD (OR 4.9; P =.001)
  • 3.8% of adolescents without a mood disorder met criteria for PTSD.

We also found that comorbid PTSD was associated with a 4.5-fold higher risk of a suicide attempt, even after we controlled for BPD diagnosis. When we controlled for the presence of other concurrent anxiety disorders, the likelihood of an adolescent with PTSD having attempted suicide remained significant (OR 3.4; P=.023). This finding suggests that PTSD is an independent risk factor for a suicide attempt.

An adult sample. We then focused on adults meeting criteria for MDD or BPD. In a study of 187 consecutively presenting affectively ill patients, we used the SCID to screen for multiple anxiety disorders including PTSD.13 Lifetime—as opposed to intra-episode—PTSD prevalence was 23.8% among the 118 patients with MDD and 62.3% among the 69 patients with BPD. A patient with BPD was 5 times more likely to have PTSD than a patient with MDD (OR 5.3; P < .0001). The most common cause of trauma leading to PTSD was sexual molestation or rape as a child or adolescent in this predominantly female Latino population.

Populations at risk for PTSD

The prevalence of PTSD in clinical samples varies, depending on the population studied. For instance, women are at much higher risk for developing PTSD than men, even in comparisons where men are exposed to a greater number of traumatic events and analyses control for differences in the prevalence of sexual abuse. The gender difference is greater if the trauma occurs during childhood.14 Essentially all patients in our adolescent and adult studies developed PTSD in response to childhood or adolescent sexual trauma.12,13

A population exposed to a high rate of violent crime would be expected to show a higher PTSD prevalence than one exposed to substantially less violence. The base rate of PTSD also is much higher in affectively ill patients than in the general population.

An analysis by Otto et al15 found a 16% lifetime prevalence of concomitant PTSD in 1,214 persons with BPD (not the manifold forms within the bipolar spectrum). Oquendo et al16 reported a 25.7% lifetime prevalence of PTSD in 230 patients with a history of MDD. Other epidemiologic2 and clinical studies12,13 suggest a considerably higher base rate of PTSD among persons with bipolar disorders than those with MDD.

The method of ascertaining the presence of this disorder may be another variable affecting the reported PTSD prevalence. Persistent avoidance—including “efforts to avoid thoughts, feelings, or conversations associated with the trauma”—is a diagnostic feature of PTSD.10 Researchers and clinicians who do not intentionally screen patients for PTSD are not likely to detect it. Determining the true prevalence of PTSD requires empathic inquiry about exposure to traumatic events.

PTSD screening

Humans are remarkably resilient, and most persons exposed to major trauma are thought not to develop PTSD. However, in my experience, because PTSD appears to be common among persons with affective illness, determining whether such patients have been traumatized is important for prognosis and treatment selection.

To get started, you could create a 1-page form to record traumatic events and identify features of PTSD according to DSM-IV-TR criteria (Checklist).10 PTSD screening without a form can become second nature with practice; an experienced clinician can screen a traumatized patient for the disorder within 3 to 5 minutes.

When screening for a history of trauma, ask patients in a straightforward manner if they have:

  • been victims of violent crimes
  • witnessed violent crimes
  • been exposed to events in which people could have suffered grave injury
  • experienced emotional, physical, or sexual abuse.

A person who has experienced emotional abuse but not physical or sexual abuse cannot meet DSM-IV-TR criterion A and therefore does not meet full criteria for PTSD. Many emotionally abused persons meet criteria B through F, however, and they are most reasonably managed similarly to persons who also meet criterion A. When formulating a treatment plan, I recommend using clinical judgment rather than rigid adherence to DSM-IV-TR.


DSM-IV-TR diagnostic criteria for posttraumatic stress disorder


Criterion A. The person has been exposed to a traumatic event in which both of the following have been present:

1. The person has experienced, witnessed, or been confronted with an event or events that involve actual or threatened death or serious injury, or a threat to the physical integrity of oneself or others

2. The person’s response involved intense fear, helplessness, or horror


Criterion B. The traumatic event is persistently re-experienced in at least 1 of the following ways:

1. Recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions

2. Recurrent distressing dreams of the event

3. Acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback episodes, including those that occur upon awakening or when intoxicated)

4. Intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event

5. Physiologic reactivity upon exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event


Criterion C. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by at least 3 of the following:

1. Efforts to avoid thoughts, feelings, or conversations associated with the trauma

2. Efforts to avoid activities, places, or people that arouse recollections of the trauma

3. Inability to recall an important aspect of the trauma

4. Markedly diminished interest or participation in significant activities

5. Feeling of detachment or estrangement from others

6. Restricted range of affect

7. Sense of foreshortened future


Criterion D. Persistent symptoms of increasing arousal (not present before the trauma), indicated by at least 2 of the following:

1. Difficulty falling or staying asleep

2. Irritability or outbursts of anger

3. Difficulty concentrating

4. Hypervigilance

5. Exaggerated startle response

Criterion E. Duration of disturbance (symptoms in B, C, and D) is >1 month

Criterion F. Disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning

Source: Adapted from Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000

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