Comparing outcomes of adjunctive treatment in depression: aripiprazole versus bupropion.

BACKGROUND: Adjunctive therapy in depression is often used in patients with an inadequate response to antidepressant therapy. METHODS: Utilizing a chart review from a private, outpatient psychiatric clinic, patients with adjunctive medication added to their antidepressant were reviewed. Demographic information, diagnoses, medication history, and QIDS SR16 depression scores were collected and recorded at each visit and entered into a database. RESULTS: Significant reductions were observed in the QIDS score of aripiprazole (n=70) and bupropion (n=83) patients after the first visit. At the first visit, 70% of aripiprazole patients had lower QIDS score compared to baseline visit, with 17% achieving remission, whereas 66% of bupropion users had lower scores at the first visit compared to baseline visit, with 23% achieving remission. At the end of the observation period 50% of patients on aripiprazole achieved remission compared to 33% of bupropion patients. Both groups of patients had significant reductions in their QIDS symptom scores of sadness, concentration, and general interest. In addition, aripiprazole patients had a decrease in the thoughts of death and suicide score while bupropion patients had decreases in the low energy score. None of the differences in QIDS line-item scores between aripiprazole and bupropion patients were statistically significant. LIMITATIONS: This study was a small scale, retrospective study that did not have a placebo control group. CONCLUSION: Aripiprazole and bupropion were comparable in significantly lowering patients' QIDS SR16 scores and helping over 50% of the patients achieve remission. Differences in line-item QIDS score were also observed.

Lower frequency of antidepressant use in patients on renin-angiotensin-aldosterone system modifying medications.

Both hypertension and depression are common disorders which may both involve components of the hypothalamic-pituitary-adrenal axis system and the Renin-Angiotensin-Aldosterone System (RAAS). These observations, coupled with growing evidence that RAAS-active drugs may have anti-depressant properties prompted us to study the frequency of anti-depressant medication usage in the patients receiving RAAS-active agents. A chart review was performed on 378 patients who were seen during a 3-month period in a primary care clinic and who were diagnosed with hypertension. Demographic information and data on the rates of co-administration of antihypertensive and anti-depressant medications was collected. Overall, 23.7% of the sample was on an antidepressant. 20% of the patients taking a RAAS-modifying medication were on an antidepressant, compared to 34% of those not taking a RAAS-modifying medication (Χ(2) = 8.88, P = 0.003). The patients taking a beta-blocker alone had the highest rate of antidepressant usage (40%). The use of RAAS-modifying medications was associated with an even lower rate of anti-depressant usage in males compared with females. It was also observed that the patients taking an additional diuretic had a significantly lower rate of antidepressant use (17.6%, Χ(2) = 5.81, P = 0.016) compared with the patients not taking a diuretic. The patients being treated with an ACE inhibitor or ARB showed significantly lower rates of antidepressant usage. The data is supportive of the hypothesis that these agents may possess anti-depressant effects.

Maltreated children's memory: accuracy, suggestibility, and psychopathology.

Memory, suggestibility, stress arousal, and trauma-related psychopathology were examined in 328 3- to 16-year-olds involved in forensic investigations of abuse and neglect. Children's memory and suggestibility were assessed for a medical examination and venipuncture. Being older and scoring higher in cognitive functioning were related to fewer inaccuracies. In addition, cortisol level and trauma symptoms in children who reported more dissociative tendencies were associated with increased memory error, whereas cortisol level and trauma symptoms were not associated with increased error for children who reported fewer dissociative tendencies. Sexual and/or physical abuse predicted greater accuracy. The study contributes important new information to scientific understanding of maltreatment, psychopathology, and eyewitness memory in children.

Elevated serum copper levels in women with a history of post-partum depression.

Previous observations suggested that there may be an association between elevated serum copper (Cu) levels and post-partum depression (PPD). In this study, we examined Zn and Cu levels in women with completed pregnancies who had a history of PPD and compared them to women who did not have depression, and to women who reported having been depressed, but without a history of PPD. Cu levels were significantly higher in women having a history of PPD compared both to non-depressed women and to depressed women without a history of PPD. The mean serum Cu level of 78 women with a history of PPD was 131+/-39microg/dL compared with 111+/-25microg/dL in 148 women without such a history, and 106+/-20microg/dL in non-depressed controls (p<0.001). Zn levels did not differ across the three groups. Cu/Zn ratios were significantly higher in the PPD-history-positive group, due to the significant differences in Cu levels. Cu and Zn levels were not significantly different in depressed and non-depressed men, nor between non-depressed women and non-depressed men. Depressed women had higher Cu, but not Zn, levels compared with men. The nature of the association between elevated Cu values and PPD is, as yet, unknown; however Cu has roles in a variety of physiological systems that may be implicated in the development of PPD.

Fluoxetine, smoking, and history of major depression: A randomized controlled trial.

The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine initially enhanced cessation for H+ smokers (p = .02) but subsequently impaired cessation regardless of depressive history. Six months after quit date, fluoxetine-treated participants were 3.3 times more likely to be smoking (p = .02). Further research is warranted to determine why high-dose fluoxetine produces continuing effects that oppose tobacco abstinence.

Effect of tryptophan depletion on smokers and nonsmokers with and without history of major depression.

BACKGROUND: Serotonergic dysregulation is posited to contribute to comorbidity between nicotine dependence and depression. We tested whether acute tryptophan depletion (ATD) triggers depressive symptoms in euthymic, unmedicated smokers and nonsmokers with and without history of major depressive disorder (MDD). METHODS: Acute tryptophan depletion and taste-matched placebo challenges were administered double-blind in counter-balanced order. Participants were four groups of volunteers hypothesized to be of increasing affective vulnerability as follows: nonsmokers lacking recurrent personal and familial history of MDD (n = 20), smokers lacking recurrent personal and familial history of MDD (n = 21), nonsmokers with history of recurrent personal and familial MDD (n = 16), and smokers with recurrent personal and familial history of MDD (n = 16). Depression, dysphoric mood, and plasma amino acids were measured at baseline and around the time of peak depletion. RESULTS: Depressive symptom response to ATD was heightened significantly by history of MDD (p < .001) and marginally by smoking (p = .09). Smoking seemed to magnify the ATD response of those with a history of MDD (effect size = .63) but had no effect on those without MDD history (effect size = .06). CONCLUSIONS: Depressive symptom response to serotonergic challenge is exaggerated in unmedicated, euthymic adults with recurrent personal and familial vulnerability to MDD, perhaps especially if they also smoke.

Frontal alpha power asymmetry in aggressive children and adolescents with mood and disruptive behavior disorders.

Building on prior research, which has suggested a relationship between aggression and left frontal activity, our study tested the hypothesis that proneness to impulsive aggression would be related to relative left frontal overactivation. EEG one-hertz resting alpha power frontal asymmetry was examined in 65 pediatric male psychiatric patients with a history of impulsive aggression and comorbid mood and disruptive behavior disorders. The strongest finding, which emerged from this analysis, was a finding of relative increases in left frontal activity compared with right frontal activity. The results also indicated that greater left frontal activity correlated positively with the severity of psychiatric disturbance. These findings suggest that relative increases in left frontal activity may be related to a locus of neurophysiological disruption associated with psychopathology characterized by behavioral and affective disinhibition. Results are discussed within a model of behavioral inhibition system-behavioral activation system theory.

Selective numbing and hyperarousal in male and female Bosnian refugees with PTSD.

Emotional numbing is an important symptom of PTSD, but it is not clear whether it affects both positive and negative affect equally or not. To address this question we administered Lang's Looking at Pictures test, in which a series of pictures are rated for valence (pleasant-unpleasant) and arousal (high-low), to 10 male and 11 female Bosnian refugees suffering from PTSD (DSM-IV criteria) and to control groups of 11 male and 10 female Bosnian refugees with similar trauma exposure but without PTSD or any other major mental illness. The mean valence ratings for unpleasant, neutral, and pleasant pictures of both PTSD and control males and females were similar to normal ratings. Likewise, the mean arousal ratings for unpleasant, neutral, and pleasant pictures of both male and female controls were similar to normals, with both unpleasant and pleasant pictures rated more arousing than neutral pictures. In contrast, in both males and females with PTSD pleasant pictures were rated as almost completely non-arousing. Thus, in Bosnian refugees affective numbing is seen primarily with pleasant or positive stimuli.

Effects of acute tryptophan depletion on negative symptoms and smoking topography in nicotine-dependent schizophrenics and nonpsychiatric controls.

We studied the effect of acute tryptophan depletion (ATD), which transiently reduces brain serotonin, on negative symptoms and cigarette smoking topography in schizophrenic smokers. Nicotine-dependent schizophrenics (n=11) and nonpsychiatric controls (n=8) were examined after ingesting comparable mixtures that do and do not deplete plasma tryptophan. Tryptophan-depleting and placebo mixtures were administered double-blind and in counterbalanced order. Conditions were separated by a 1-week interval. Psychopathologic symptoms (negative symptoms, depression) and smoking topography (time to first puff, number of puffs per cigarette, puff duration, interpuff interval, cigarette duration, and percentage of cigarette smoked) were measured before ingestion and again beginning 5 h after each mixture, corresponding to the time of maximal tryptophan depletion. Analyses were conducted using repeated measures analyses of variance (psychopathologic symptoms) and analyses of covariance (smoking topography) controlling for cigarette length. We found that ATD influenced smoking topography in both schizophrenics and nonpsychiatric controls in a manner suggestive of increased desire to smoke. Schizophrenics exhibited increased puff duration and decreased cigarette duration. Controls displayed increased puff duration. ATD did not produce changes in negative symptoms or depression. Compromising brain serotonin via ATD appears to intensify smoking behavior in nicotine-dependent individuals directly, rather than indirectly through changes in either mood or psychopathologic symptoms.

Double-blind trial of the effects of tryptophan depletion on depression and cerebral blood flow in smokers.

Studies of clinically depressed patients have documented left frontal lobe hypoactivity. Smokers also show an increased prevalence of depression and evidence that nicotine normalizes qEEG indices of left frontal lobe activity. Tryptophan depletion (TD) has been shown to increase negative mood in smokers, particularly those with recurrent depression. Thus, in smokers, we expected that increased depression during TD would be associated with decreased cerebral blood flow, specifically in the left frontal lobe. Hamilton depression scores and relative regional cerebral blood flow (rCBF) were measured with SPECT using (99m)Tc-hexamethylpropyleneamineoxime in seven smokers after TD and after a control procedure. Decreased bilateral cerebral blood flow to the inferior frontal (IF) lobe following TD relative to placebo was associated with increased depressed mood (r= -.653, P<.05). Among smokers, a decrease in brain serotonin is associated with increased depressed mood and with focal bilateral decreases in IF activity. Chronic nicotine exposure appears to be associated with cortical responses suggestive of depressive vulnerability.

Biochemical and psychiatric predictors of Li(+) response and toxicity in Li(+)-treated bipolar patients.

BACKGROUND: It has not been determined whether biochemical or psychological variables predict clinical response and toxicity to Li(+) treatment. METHODS: From 30 Li(+)-treated bipolar patients, we measured biochemical variables in red blood cells (RBCs) that encompassed the cell membrane abnormality and the Li(+)/Mg(2+) competition mechanism. Psychiatric measures of depression, mania, and side effects of Li(+) toxicity were correlated with these biochemical variables. Physician classification of Li(+) response and toxicity for each patient were used for determining whether significant differences in biochemical variables and psychiatric measures existed between full and partial responders, and as well as toxic and non-toxic Li(+)-treated bipolar patients. RESULTS: Serum [Li(+)] ([Li(+)]e), the ratio of intracellular RBC to serum Li(+), [Li(+)]i/[Li(+)]e, and phosphatidylcholine shared moderate proportions of variance (10-15%) with several of the psychiatric measures. Physician assessment of full response was predicted by higher levels of [Li(+)]e and lower scores on the Hamilton Slowing subscale (95.6% accuracy), whereas higher lithium-binding constants and higher Hamilton total scores perfectly predicted physician classification of partial response. Higher scores on Hamilton Slowing subscale and General Side Effects (GSE) scale were strongly predictive of physician classified Li(+) toxicity (80% accuracy), whereas lower levels of [Li(+)]e and lower scores on the Hamilton Symptom Severity subscale perfectly predicted physician rated non-toxicity in these patients. CONCLUSIONS: We found distinct [Li(+)]e levels that predict response and/or toxicity. Specifically, when [Li(+)]e was in the range of 0.93-1.42 mM, full response without toxicity was predicted; higher values predicted toxicity; lower values predicted partial response.

Testing competing path models linking the biochemical variables in red blood cells from Li+-treated bipolar patients.

OBJECTIVES: Red blood cells (RBCs) from Li+-treated bipolar patients have shown abnormalities in intracellular Li+ concentration ([Li+]i), Na+/Li+ exchange rates, and membrane phospholipid levels. Based on Li+-loaded RBC studies, we hypothesized that Li+-treated bipolar patients also have varied intracellular free Mg2+ concentrations ([Mg2+]f) as compared with normotensive patients. We addressed how these experimentally determined values are intercorrelated. Assuming that Li+ treatment alters these biochemical parameters, we provide hypothetical pathways based upon structural equation modeling statistics. METHODS: In RBCs from 30 Li+-treated bipolar patients, we determined [Li+]i, serum [Li+] ([Li+]e), Na+/Li+ exchange parameters, membrane phospholipid levels, [Mg2+]f, and Li+ membrane binding affinities. Comprehensive statistical analyses assessed correlations among the biochemical data. We used path analysis statistics to propose potential pathways in which the data were correlated. RESULTS: We found significant correlations within the three Na+/Li+ exchange parameters and percentage composition of the membrane phospholipids. Additional correlations existed between [Mg2+]f and Vstd, Km, or phospholipid composition, between [Li+]i and percentage of phosphatidylcholine, and between percentage of phosphatidylserine and Km. Based on these findings, we hypothesized and statistically determined the most probable pathway through which these parameters were intercorrelated. CONCLUSIONS: Significant correlations existed between the biochemical parameters that describe the cell membrane abnormality and the Li+/Mg2+ competition hypotheses. Using path analysis statistics, we identified a biochemical pathway by which Li+ may assert its cellular effects. This study serves as an illustrative example how path analysis is a valuable tool in determining the direction of a certain biochemical pathway.