Adjunctive risperidone treatment in post-traumatic stress disorder: a preliminary controlled trial of effects on comorbid psychotic symptoms.

Positive and negative symptoms of psychosis may be common in patients with chronic post-traumatic stress disorder (PTSD), but few studies have investigated the use of antipsychotic agents in these patients. This preliminary study examined the potential efficacy of risperidone in treating psychotic symptoms associated with chronic PTSD. In a 5-week, prospective, randomized, double-blind, placebo-controlled trial, adjunctive risperidone treatment was assessed in 40 combat veterans with chronic PTSD and comorbid psychotic features. Most patients were receiving antidepressants and some other psychotics with doses of concurrent medications held constant for at least 1 month prior to and during the study. Thirty-seven patients completed at least 1 week of treatment with risperidone or placebo. The Positive and Negative Syndrome Scale (PANSS) and the Clinician Administered PTSD Scale (CAPS) were used to assess symptoms. The PANSS was the primary outcome measure. At treatment endpoint, risperidone-treated patients showed a significantly greater decrease from baseline, albeit modest, in psychotic symptoms (PANSS total scores) than placebo-treated patients (P < 0.05). CAPS ratings declined significantly in both groups but did not differ significantly between groups. However, CAPS re-experiencing subscale scores had greater improvement in the risperidone-treated patients at week 5 (P < 0.05, completer analysis) with a trend towards greater improvement versus placebo a endpoint (P < 0.1, LOCF). Risperidone was well tolerated with minimal extrapyramidal symptoms. These preliminary results support studying the potential efficacy of risperidone for treating global psychotic symptoms associated with chronic PTSD with a suggestion that core re-experiencing symptoms may also be responsive. Further research using randomized, controlled trial designs in larger patient groups are needed to define more adequately the role of risperidone and other atypical agents in PTSD.

Gabapentin in PTSD: a retrospective, clinical series of adjunctive therapy.

Posttraumatic stress disorder (PTSD) symptoms may improve significantly with antidepressant medications, however some phenomena often remain refractory to the most commonly used treatments. Frequently, sleep disturbances, such as insomnia and nightmares, are symptoms of PTSD that are refractory to antidepressant treatment. Gabapentin, a novel anticonvulsant agent, has been of interest as a potential anxiolytic agent, but has not been evaluated in PTSD. We reviewed records of 30 consecutive patients who had been diagnosed with PTSD according to structured interviews and had received gabapentin as an adjunctive medication. For each patient, the target symptoms that led to the initiation of gabapentin treatment were identified. Using the most recent clinical data available, the change in target symptom severity following treatment was rated as unimproved, mildly improved, moderately improved, or markedly improved. The gabapentin was often first prescribed to facilitate sleep. The majority (77%) of patients showed moderate or greater improvement in duration of sleep, and most noted a decrease in the frequency of nightmares. The dose range was 300-3600 mg/day. Sedation and mild dizziness were the most commonly reported side effects. This retrospective study suggests that gabapentin may improve in particular sleep difficulties and also other symptoms associated with chronic PTSD. Prospective, controlled studies are needed to further investigate the effects of gabapentin on insomnia, nightmares, and other core PTSD symptoms.

Apparent symptom overreporting in combat veterans evaluated for PTSD.

Psychometric studies have consistently shown that combat veterans evaluated for posttraumatic stress disorder (PTSD) appear to overreport psychopathology as exhibited by (a) extreme and diffuse levels of psychopathology across instruments measuring different domains of mental illness, and (b) extreme elevations on the validity scale of the MMPI-MMPI-2, in a "fake-bad" direction. The phenomenon of this ubiquitous presentational style is not well understood at present. In this review we describe and delineate the assessment problem posed by this apparent symptom overreporting, and we review the literature regarding several potential explanatory factors. Finally, we address conceptual and practical issues relevant to reaching a better understanding of the phenomenon, and ultimately the clinical syndrome of combat-related PTSD, in both research and clinical settings.

Clinical presentations of posttraumatic stress disorder across trauma populations: a comparison of MMPI-2 profiles of combat veterans and adult survivors of child sexual abuse.

This investigation examined differences in symptom patterns of two different trauma samples using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). MMPI-2s of 122 male combat veterans seeking outpatient treatment for combat-related PTSD were compared with those of 64 PTSD-diagnosed adults seeking outpatient treatment for the effects of child sexual abuse (CSA). We examined variables related to degree of health concerns, depression, somatization, anger and hostility, masculine-feminine traits, paranoid ideation, anxiety, difficulties thinking and concentrating, elevated mood, and social introversion, as well as test-taking attitude. MANOVAs revealed between-group differences on several variables. However, when analyses controlled for the effect of age, nearly all differences disappeared; the only remaining difference was in a scale measuring anger. Thus, it appears CSA survivors and combat veterans are much more similar than different in their clinical presentation on the MMPI-2. Conceptual issues in the assessment of PTSD are discussed.

Psychotic features in chronic posttraumatic stress disorder and schizophrenia: comparative severity.

Psychotic features are frequent in combat veterans with chronic posttraumatic stress disorder (PTSD), may correlate with severity of PTSD symptoms, and may reflect a distinct subtype of the disorder. These psychotic features include auditory and visual hallucinations and delusional thinking that is usually paranoid in nature. Psychotic features may be under-recognized in chronic PTSD because patients are reluctant to report these symptoms and because they may not have overt changes in affect or bizarre delusions characteristic of other psychoses, e.g., schizophrenia. To further assess these phenomena, we compared clinical ratings on the Positive and Negative Syndrome Scale (PANSS) and other assessments, including the Clinical Global Impression Scale and the Structured Clinical Interview with Psychotic Screen, in veterans meeting DSM-IV criteria for chronic PTSD with well-defined comorbid psychotic features (N = 40) or chronic schizophrenia (N = 40). The patients with schizophrenia had modestly higher composite PANSS scores and positive symptom scores although average scores in both groups were moderate to severe in intensity. Negative symptom and general psychopathology subscale scores were comparable in both groups. Regarding specific positive symptoms, hallucinations were comparable between groups in severity; however, schizophrenia patients had slightly more intense delusions and conceptual disorganization. These data further validate the occurrence of positive as well as negative symptoms of psychosis in chronic PTSD in a range of severity that may approach that of patients with schizophrenia. Although meeting DSM-IV criteria for two different major psychiatric disorders, these two patient populations were remarkably similar with respect to not only positive but also negative symptoms.

Psychotic features and illness severity in combat veterans with chronic posttraumatic stress disorder.

BACKGROUND: Psychotic symptoms may be present in up to 40% of patients with combat-related posttraumatic stress disorder (PTSD). In this study, we hypothesized that severity of psychotic symptoms would also reflect severity of PTSD symptoms in patients with well-defined psychotic features. METHODS: Forty-five Vietnam combat veterans with PTSD but without a primary psychotic disorder diagnosis underwent a Structured Clinical Interview for DSM-III-R with Psychotic Screen, and the Clinician Administered PTSD Scale (CAPS). Patients identified as having psychotic features (PTSD-P), (n = 22) also received the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). RESULTS: There was a significant positive correlation between the CAPS and PANSS global ratings (p < .001) and the HDRS and PANSS (p < .03) in the PTSD-P patients. Many CAPS and PANSS subscales also demonstrated significant intercorrelations; however, the CAPS-B subscale (reexperiencing) and the PANSS positive symptom scale were not correlated, suggesting that psychotic features may not necessarily be influenced or accounted for by more severe reexperiencing symptoms. Fifteen (68%) of the PTSD-P patients had major depression (MDD). Both CAPS and PANSS ratings were significantly higher in the PTSD-P patients with comorbid MDD. CONCLUSIONS: As postulated, patients with more severe psychosis ratings are likely to have more severe PTSD disease burden if psychotic features are present. This study further documents the occurrence of psychotic features in PTSD that are not necessarily due to a primary psychotic disorder, suggesting that this may be a distinct subtype; however, a significant interaction likely exists between PTSD, depression, and psychotic features.

Potential role of the anterior cingulate cortex in PTSD: review and hypothesis.

Many symptoms of PTSD represent conditioned responses to stimuli associated with a traumatic experiences. In this review, we propose that the anterior cingulate--a brain region that appears to be involved in fear-conditioning--is dysfunctional in PTSD, thus facilitating exaggerated emotional and behavioral responses (hyperarousal) to conditioned stimuli. Preclinical studies suggest that the anterior cingulate may serve a critical gating function in modulating conditioned fear responses. As such, this region would be a key component of a neural circuit involved in the pathophysiology of PTSD. An amygdala-locus coeruleus-anterior cingulate circuit may be consistent with evidence for chronic noradrenergic activation documented in PTSD patients. According to this model, efferent noradrenergic projections from the locus coeruleus may dampen anterior cingulate function. This in turn would allow myriad external or internally driven stimuli to produce the exaggerated emotional and behavioral responses characteristic of PTSD. If confirmed in future research, cingulate dysfunction would have important theoretical and treatment implications.

Response to venlafaxine in a previously antidepressant treatment-resistant combat veteran with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is frequently treated with antidepressant medications, especially the newer selective serotonergic antidepressants which have documented efficacy in PTSD. Analogous to depression, however, some PTSD patients may not have a satisfactory response to these agents. This case report describes a PTSD patient who did not respond to several serotonergic antidepressants, but did improve with venlafaxine which has both noradrenergic and serotonergic properties.

Plasma dopamine beta-hydroxylase activity in psychotic and non-psychotic post-traumatic stress disorder.

Recognition and treatment of comorbid chronic psychotic symptoms in post-traumatic stress disorder (PTSD) has become of increasing clinical interest. Altered dopamine beta-hydroxylase (DBH) activity has been reported in mood disorders. Plasma DBH is reduced in major depression with psychosis and elevated in bipolar disorder with psychosis compared with their respective non-psychotic diagnostic groups. DBH is likely a trait marker with interindividual variations secondary to genetic polymorphism. We therefore evaluated DBH activity in PTSD patients with and without psychotic features and compared these groups with age- and gender-matched control subjects. Vietnam combat veterans with PTSD (n = 19) (including patients with and without psychotic features) and normal control subjects (n = 22) had plasma DBH enzyme activity assayed photometrically. DBH was significantly higher in patients with PTSD with psychotic features than in patients without psychotic features (80.6 +/- 13.4 vs. 42.1 +/- 7.3 mM/min, P < 0.01) and was also higher than normal control subjects (46.12 +/- 4.93, P < 0.01). Plasma DBH activity may differentiate psychotic and non-psychotic subtypes of PTSD. The observed changes are, interestingly, opposite to those seen in psychotic depression but comparable to psychotic bipolar disorder. Since DBH is a genetic marker, this may reflect individual vulnerabilities to develop psychosis in the context of trauma.

Psychotic features and combat-associated PTSD.

Psychotic symptoms and psychotic disorder diagnoses have occasionally been reported in association with chronic posttraumatic stress disorder (PTSD). Although psychotic features may be related to core PTSD symptoms, i.e., part of the reexperiencing phenomena, it is possible that they are secondary to certain comorbid disorders which are also prevalent in this patient population, e.g. major depression or substance abuse. In a prospective study, combat associated PTSD patients (n = 25) were administered clinical ratings, including the Structured Clinical Interview for DSM-III-R with psychotic screen (SCID-P), Clinician Administered PTSD Scale (CAPS) and the Impact of Events Scale (IES). Thirty-six percent (n = 9) endorsed psychotic symptoms with associated comorbidity including: major depressive episode, bipolar disorder, alcohol or polysubstance abuse panic disorder, and phobias. All but one of the patients with psychotic features also met criteria for major depressive episode. None had a primary psychotic disorder diagnosis. There were no significant differences in total CAPS scores between patients with or without psychotic features (82.6 +/-0 17.6 versus 75.3 +/- 22.4, p ns), nor for the different symptom cluster subscales. There were also no differences in the IES scores between groups (34.8 +/- 10 versus 32.6 +/- 10 p ns). This suggests that these psychotic features may not necessarily reflect severity of PTSD symptoms. PTSD may share a common diathesis with mood disorders including psychotic depression. Further study is needed of these phenomena.

Plasma dopamine and norepinephrine correlations with psychomotor retardation, anxiety, and depression in non-psychotic depressed patients: a pilot study.

The relationship of plasma catecholamine levels to severity of depression and psychomotor retardation was examined in 12 male inpatients who met criteria for major depressive episode. Psychomotor retardation was measured with the Psychomotor Retardation Rating Scale (PRRS), and depression was assessed with the Hamilton Rating Scale for Depression (HRSD). Blood samples for biochemical measurements were obtained from drug-free patients at approximately 09:00 h. Plasma dopamine (DA) levels correlated significantly with the HRSD total score and the anxiety subscale score. Plasma norepinephrine (NE) levels demonstrated a trend toward a negative correlation with the HRSD total score. Neither plasma DA nor NE levels showed a significant correlation with either the global PRRS score or the cognitive or motor subscale score. HRSD scores failed to correlate with the PRRS scores.

Plasma prolactin in schizophrenia subjects treated with Seroquel (ICI 204,636).

Treatment with standard antipsychotic medications causes side effects such as hyperprolactinemia and extrapyramidal symptoms. Because these side effects can cause noncompliance with antipsychotic medication and consequent relapse, they add to the morbidity of schizophrenia. A compound with antipsychotic efficacy but without the side effects of standard antipsychotic agents would improve compliance and treatment outcomes and enhance quality of life. Improved compliance, reduced relapse, and decreased hospitalization would also reduce the cost of treatment of schizophrenia. Seroquel (ICI 204,636), an atypical antipsychotic compound in Phase III development, was found to be well tolerated and effective in treating subjects with DSM-III-R schizophrenia in three Phase II clinical trials. Analysis of plasma prolactin concentrations obtained during these trials revealed that ICI 204,636 did not differ from placebo in its effect on plasma prolactin after up to 6 weeks of treatment; no significant difference was found in the degree of decline of plasma prolactin levels when subjects treated with ICI 204,636 and placebo were compared. A significant difference was found, however, between ICI 204,636- and chlorpromazine-treated subjects; prolactin levels in ICI 204,636-treated subjects fell to a greater degree than they did in chlorpromazine-treated subjects, however in all three trials, ICI 204,636 did not cause sustained elevation of prolactin.

Exacerbation of posttraumatic stress disorder symptoms with medical illness.

Chronic posttraumatic stress disorder (PTSD) may increase the risk for associated psychiatric and medical illnesses. In turn, the onset of medical illness may result in an exacerbation of PTSD symptoms leading to excessive or maladaptive psychological and physiological reactions. Five combat veterans with PTSD and medical disease are presented to illustrate this potential for worsening of PTSD with concurrent medical illness. Health care workers in general hospital settings should be aware of unique psychological vulnerabilities in PTSD patients. Prospective studies are needed to assess the impact of medical comorbidity on the course of PTSD.

Clonazepam-related sexual dysfunction in male veterans with PTSD.

Medication-induced sexual dysfunction can significantly interfere with patients' quality of life and lead to poor compliance. This retrospective study examined the records of 100 male veterans with post-traumatic stress disorder (PTSD) selected in alphabetical order from an active treatment file of 230 patients. Forty-two patients had received clonazepam (mean maximum dose: 3.4 +/- 1.6 mg/day) at some point during their treatment. Of these, 18 (42.9%) complained of significant sexual dysfunction (primarily erectile dysfunction). Eighty-four patients received diazepam (mean maximum dose: 52.1 +/- 29.7 mg/day), nine received alprazolam (mean maximum dose: 5.2 +/- 2.8 mg/day) and eight received lorazepam (mean maximum dose: 3.8 +/- 2.4 mg/day). None of these patients complained of sexual dysfunction during treatment with these three other benzodiazepines. Our findings suggest that benzodiazepines, particularly clonazepam in the current study, can be a cause of sexual dysfunction in many male patients. Prospective studies comparing the overall clinical utility of various benzodiazepines are indicated in this and other clinic populations.