Divalproex in posttraumatic stress disorder: an open-label clinical trial.

Posttraumatic stress disorder (PTSD) is characterized by intrusive, avoidance, and hyperarousal symptoms. This study was conducted to investigate the effectiveness of divalproex in reducing PTSD symptoms, depression, and anxiety in patients with PTSD. Sixteen patients with a DSM-IV diagnosis of PTSD at the Albuquerque VAMC outpatient PTSD treatment program received an open-label trial of divalproex. The patients were evaluated at baseline and at 8 weeks by a trained rater using the Clinician Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A). Plasma valproate levels were measured at the 8-week post-treatment assessment. Three patients stopped the medications due to side effects. Intrusion and hyperarousal symptoms decreased significantly, while no significant change was seen in avoidance/numbing symptoms. Depressive symptoms, as measured by the HAM-D, unexpectedly decreased at post-treatment assessment. HAM-A scores also decreased significantly. Controlled trials are needed to further study the efficacy of divalproex in the treatment of PTSD.

Bupropion treatment in veterans with posttraumatic stress disorder: an open study.

This study was designed to investigate the efficacy of the antidepressant drug bupropion in the treatment of posttraumatic stress disorder (PTSD). Seventeen male combat veterans with chronic PTSD were treated with bupropion in an open-label fashion for 6 weeks. Patients were evaluated with the Clinical Global Impressions Scale for Improvement (CGI-I) at follow-up and rated blindly at baseline and posttreatment with the Clinician Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety. Three patients discontinued bupropion prematurely because of side effects. Of the remaining 14 patients, 10 were classified as treatment responders by the CGI-I. HAM-D scores decreased significantly from baseline to follow-up. The improvement seen in hyperarousal symptoms was significant but was less significant than the change in depressive symptoms. There was no significant change in Intrusion, Avoidance, or total CAPS scores. It was concluded that bupropion was well tolerated. Patients who had experienced sexual dysfunction with selective serotonin reuptake inhibitors reported no complaints during bupropion treatment. Bupropion decreased depressive symptoms and most patients reported global improvement, although PTSD symptoms remained mostly unchanged. Controlled trials should further clarify the role of bupropion in the treatment of PTSD.

Spontaneous brain magnetic activity in schizophrenia patients treated with aripiprazole.

This magnetoencaphalographic (MEG) study was conducted as part of a multicenter clinical trial to study the efficacy of aripiprazole. Participants included 5 DSM-IV schizophrenia subjects and 10 age-matched normal controls. The schizophrenia subjects underwent a second MEG recording after 8 weeks of open-label treatment with aripiprazole. Overall, control subjects showed no abnormal spontaneous magnetic brain activity. At washout, 3 patients showed increased delta and theta activity along with paraxosymal bitemporal slow waves. In 2 of these patients, the slow waves were generated in the superior temporal plane, as determined by dipole modeling. In the third patient, the slow waves appeared to have been generated at multiple regions throughout the temporal and inferior parietal lobes. As a group, schizophrenia patients, when compared with normal controls, demonstrated significant decreases in alpha peak frequency and power. Following treatment, aripiprazole had a significant normalizing effect on delta and theta activity. Patients on aripiprazole continued to demonstrate significant abnormalities in alpha frequency and power.

Family psychoeducational support groups in Spain: parents' distress and burden at none-month follow-up.

Forty-one mothers and twenty-seven fathers agreed to participate in a 6-week, low-cost, multiple-family psychoeducational intervention in Spain. Their knowledge acquisition, subjective distress, annoyance at patient's behavior, perception of social impact of the patient's illness, expectations about patient's recovery, and family burden were measured before and after the intervention and at 9-month follow-up. Ninety-three percent of the fathers and 78% of the mothers attended four or more classes. Although parents acquired a significant amount of knowledge about the illness, no significant score differences were found immediately after the intervention or at follow-up in the other measures. However, significant father-mother differences were revealed. Compared with mothers, fathers were more optimistic throughout the study about the outcome of the illness, became more aware of the social and financial impact of the illness on the family, and reported feeling less annoyed by the patient's behavior at follow-up. The results indicate that low-cost psychoeducational multiple family groups alone do not decrease family distress and burden. These findings also suggest that psychoeducational interventions need to consider differences in gender and family roles and underline the importance of engaging fathers in treatment.

Urinary levels of 3-methoxy-4-hydroxyphenylglycol predict symptom severity in selected patients with unipolar depression.

There are preliminary biological data that support the validity of subtyping depressed patients by family history into depressive spectrum disease (DSD) and non-DSD groups. We hypothesized that a relatively homogeneous group of depressed patients might show an association between symptom severity and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG). Twenty-four patients with non-DSD depression showed a relationship between urinary levels of MHPG and the severity of several depressive symptoms. There were no associations between MHPG and symptom severity for 38 DSD patients. This study provides additional support for the validity of family history approaches to subtyping depression. The data also suggest that norepinephrine may be involved in some way in the pathogenesis of symptoms in non-DSD depression.

Low levels of MHPG in depressive spectrum patients.

There is some preliminary laboratory support for the proposed classification of depressed patients into depressive spectrum disease (DSD) and non-DSD. This study explores whether there is a difference in the levels of the norepinephrine metabolite, MHPG, in DSD and non-DSD patients. MHPG levels from 38 DSD patients were compared with 24 non-DSD patients. After controlling for the influence of age and gender on MHPG, the DSD patients had MHPG levels that were lower than non-DSD patients; 1655 +/- 90 mg/day vs. 1965 +/- 174 mg/day, respectively; P = 0.05. This study provides additional laboratory support for the DSD subtype. Possible implications of this finding are discussed.

Magnetoencephalographic assessment of spontaneous brain activity in schizophrenia.

Magnetoencephalography (MEG) offers an attractive alternative to electroencephalography (EEG) in the assessment of psychiatric patients. In this study, a whole-head biomagnetometer equipped with 122 super-cooled sensors was used to assess spontaneous neuromagnetic activity in 11 unmedicated schizophrenic patients and 8 schizophrenic patients medicated for more than 8 weeks with novel antipsychotics (5 of whom were initially studied as part of the unmedicated group). Ten normal (nonpsychiatric) controls were also examined. For each subject, 5 minutes of data were collected in an eyes-closed state. Data were visually inspected for gross MEG abnormalities, and average power spectra were calculated for the data at each sensor. No gross abnormalities were identified for control subjects. One unmedicated schizophrenic patient showed epileptiform sharp waves, and 4 showed abnormal slow waves. No gross MEG abnormalities were found for the medicated schizophrenic group (which included 3 patients who had previously shown slow waves in the unmedicated state). Spectral analyses showed that the schizophrenia patients demonstrated lower alpha power and peak frequency than controls. The data are interpreted within the context of previously reported magnetic resonance abnormalities of the thalamus.

Do low levels of MHPG in depressive spectrum patients normalize after successful treatment?

Patients with depressive spectrum disorder (DSD) have low levels of the norepinephrine metabolite, MHPG. This study examines what happens to the low levels of MHPG following improvement of depressive symptoms. Sixteen depressed patients with a family history consistent with DSD showed no change in MHPG after 6 weeks of treatment. This was true for both treatment responders and nonresponders. The lack of change in low levels of MHPG suggests that reduced norepinephrine turnover is a biological trait of DSD patients. Implications of this finding are discussed.

Family environment predictors of outcome in schizophrenic patients in Spain: a nine-month follow-up study.

This study investigates the effects of perceived family environment on clinical outcome among patients in Spain who suffer from schizophrenia. Forty-five consecutively admitted DSM-III-R schizophrenic patients were assessed monthly with the Brief Psychiatric Rating Scale during a 9-month period. Patients and parents rated the family environment through the Family Environment Scale (FES). FES factors were considered separately for each family member, since parents' and patient's perceptions of the family environment were weakly correlated. Stepwise multiple regression analysis showed that patients' perceptions of family control and intellectual-cultural orientation predicted rehospitalization. Patients' and mothers' ratings of family control and fathers' scores of conflict and moral religious emphasis predicted psychotic relapse. However, fathers' scores of family cohesion predicted higher negative symptoms. Prior admissions, age of onset and use of depot medication tended to predict outcome in conjunction with the family variables.

Relationship between 3-methoxy-4-hydroxyphenylglycol and suicide.

Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in 53 depressed women were compared to current suicidal thoughts or activity. Comparisons were also made between MHPG and past suicide attempts, number of past attempts, and seriousness of the worst attempt. There was a weak trend for current but not past suicidality to be associated with decreased MHPG levels.

Effects of single dose haloperidol administration on plasma homovanillic acid levels in normal subjects.

Homovanillic acid (HVA), an oxidative metabolite of dopamine, has been shown in a number of studies to reflect severity of symptoms and to predict response to neuroleptic treatment in schizophrenic patients. In several clinical studies, HVA levels have been shown to have a positive relationship with symptom severity and to decline over time upon treatment with antipsychotic agents. The magnitude of this decline appears to be related to the degree of symptom reduction in patients so treated. However, administration of dopamine postsynaptic antagonists should be expected to increase synaptic dopamine availability, thereby increasing HVA concentrations, according to traditional models of drug action. While in some studies, this appears to be the case, we saw no evidence of an early phase of HVA elevation after administration of 4- and 10-milligram doses of haloperidol to human volunteers. Rather, HVA levels declined during the period of absorption and attainment of peak haloperidol levels. Baseline HVA levels of 51.6 +/- 3.83 pmoles/ml and 56.8 +/- 5.70 pmoles/ml (after 4 mg and 10 mg., respectively) declined to minima of 35.6 +/- 1.67 pmoles/ml and 26.3 +/- 5.34 pmoles/ml respectively, at 3-4 hours after haloperidol administration. A trend was noted for the 10-mg dose to produce a greater decline than the 4-mg dose, which was most apparent at 4 hours after drug administration. The shape of both curves did not appear to be substantially different than expected on the basis of diurnal variation. These preliminary findings support the concept that dopamine turnover in humans is not increased and may be decreased by short-term administration of conventional neuroleptics.

Cognitive therapy and pharmacotherapy for depression. Singly and in combination.

Cognitive therapy and imipramine hydrochloride tricyclic pharmacotherapy, each singly and in combination, were compared in the treatment of nonpsychotic, nonbipolar depressed outpatients. One hundred seven patients were randomly assigned to 12 weeks of active treatment; 64 patients completed the full course of treatment. Rates of attrition were high but not differential. Cognitive therapy and pharmacotherapy did not differ in terms of symptomatic response, either in the primary analyses or in secondary analyses restricted to more severely depressed outpatients. Initial severity did predict response within pharmacotherapy alone, but not within cognitive therapy. Combining cognitive therapy with pharmacotherapy did not markedly improve response over that observed for either modality alone, although such nonsignificant differences as were evident did favor the combined treatment. Two patients died as a consequence of suicide attempts, both of which involved study medication.

Differential relapse following cognitive therapy and pharmacotherapy for depression.

Patients successfully treated during a 3-month period with either imipramine hydrochloride pharmacotherapy, cognitive therapy, or combined cognitive-pharmacotherapy were monitored during a 2-year posttreatment follow-up period. Half of the patients treated with pharmacotherapy alone continued to receive study medications for the first year of the follow-up. All other patients discontinued treatment at the end of the acute treatment phase. Patients treated with cognitive therapy (either alone or in combination with medication) evidenced less than half the rate of relapse shown by patients in the medication--no continuation condition, and their rate did not differ from that of patients provided with continuation medication. It appears that providing cognitive therapy during acute treatment prevents relapse. Whether this preventive effect extends to recurrence remains to be determined.

Pharmacy and Therapeutics committee. Cost-containment considerations.

The Pharmacy and Therapeutics committee is a frequently used mechanism for health care organizations to meet mandated standards. The control that the committee has over the formulary is often seen as a potential way of controlling the expenditures for drugs. As the Pharmacy and Therapeutics committee is the means for the clinical staff to have an effect as to what agents are available to practitioners, it is incumbent on the committee members to have a clear idea of what their role should be in cost containment. An important concept that impacts on cost is that optimal health benefit is not necessarily the result of maximum expenditure. The welfare of the patient is paramount to all in the health care field; however, it is the task of clinicians to determine what constitutes optimal health benefit and to act as agents of the patient. Clinicians must maintain patient care as their top priority. Although health care expenditures are an extremely important issue, quality of patient care cannot be subrogated to a secondary concern.

Response of depression to very high plasma levels of imipramine plus desipramine.

Forty-five depressed patients were treated with imipramine for 6 weeks. Seven of 7 patients (100%) who had plasma levels of imipramine plus desipramine greater than 500 ng/ml showed a 50% or greater improvement in Hamilton depression scores compared with 23 of 38 patients (60%) with plasma levels less than 500 ng/ml (p less than 0.057).

How does cognitive therapy work? Cognitive change and symptom change in cognitive therapy and pharmacotherapy for depression.

The effects of changes in depression-relevant cognition were examined in relation to subsequent change in depressive symptoms for outpatients with major depressive disorder randomly assigned to cognitive therapy (CT; n = 32) versus those assigned to pharmacotherapy only (NoCT; n = 32). Depression severity scores were obtained at the beginning, middle, and end of the 12-week treatment period, as were scores on 4 measures of cognition: Attributional Styles Questionnaire (ASQ), Automatic Thoughts Questionnaire (ATQ), Dysfunctional Attitudes Scale (DAS), and the Hopelessness Scale (HS). Change from pretreatment to midtreatment on the ASQ, DAS, and HS predicted change in depression from midtreatment to posttreatment in the CT group, but not in the NoCT group. It is concluded that cognitive phenomena play mediational roles in cognitive therapy. However, data do not support their status as sufficient mediators.

Does 24-h urinary MHPG predict treatment response to antidepressants? II. Association between imipramine response and low MHPG.

Thirty depressed patients collected 24-h urine samples for a 3-methoxy-4-hydroxyphenylglycol (MHPG) determination prior to imipramine treatment. Patients responding to treatment had lower levels of MHPG than did non-responders.

Does 24-h urinary MHPG predict treatment response to antidepressants? I. A review.

The ability of pretreatment 3-methoxy-4-hydroxyphenylglycol (MHPG) to predict response to various antidepressants is reviewed. MHPG appears to be a modest predictor of treatment response to imipramine but does not appear to be a reliable predictor for other antidepressants.

The association of MHPG to dexamethasone suppression test status.

The results of the dexamethasone suppression test (DST) were compared to levels of 24-hour 3-methoxy-4-hydroxyphenylglycol (MHPG) in 60 patients with unipolar depression. DST nonsuppressors had significantly higher levels of MHPG than did DST suppressors. The possible implications of this finding are discussed.