Vicente B. Tuason

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.

Family Psychoeducational Support Groups in Spain: Parents Distress and Burden at Nine-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 patients behavior, perception of social impact of the patients illness, expectations about patients 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 patients 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.

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.

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.

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.

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.

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.

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.