Enhanced ziprasidone combination therapy effectiveness in obese compared to nonobese patients with bipolar disorder.

OBJECTIVE: To assess longer-term ziprasidone effectiveness in obese and non-obese patients with bipolar disorder (BD). METHODS: Outpatients assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation and monitored with the Systematic Treatment Enhancement Program for BD Clinical Monitoring Form received open ziprasidone. RESULTS: Eighty-two patients (39 patients with BD I, 39 patients with BD II, and 4 patients with BD not otherwise specified; mean age, 41.1 years; females, 78.0%; obese, 48.8%) received ziprasidone combined with an average of 3.6 (in 74.4% at least 3) other prescription psychotropics and 1.2 prescription nonpsychotropics. Mean (median) ziprasidone final dose and duration were 134.3 (150) mg/d and 489 (199.5) days, respectively. Ziprasidone yielded in obese compared to nonobese patients less discontinuation (42.5% vs 71.4%, P = 0.01), albeit with a higher rate of addition of subsequent psychotropic medication (62.5% vs 35.7%, P = 0.03). Moreover, obese compared to nonobese patients had a higher rate of shift to final-visit euthymia (27.5% vs 0.0%, P = 0.0002), and more weight loss (-20.7 lbs vs -0.6 lbs, P = 0.001), and obese (but not nonobese) patients had significant improvements in mean Clinical Global Impression-Severity of Illness (decreased 0.6 points; P = 0.03) and Global Assessment of Functioning (increased 3.3 points, P = 0.01) scores. Weight change correlated significantly with Global Assessment of Functioning change (P = 0.047) but not with Clinical Global Impression-Severity of Illness change. Limitations are small sample size and open-label, uncontrolled, observational design. CONCLUSION: Controlled and additional observational studies seem warranted to confirm our preliminary findings suggesting ziprasidone may be more effective in obese compared to nonobese patients with BD already receiving combination pharmacotherapy.

Pilot study of the efficacy of double-blind, placebo-controlled one-week olanzapine stabilization therapy in heterogeneous symptomatic bipolar disorder patients.

BACKGROUND: Olanzapine has demonstrated efficacy in acute mania and bipolar I disorder (BDI) maintenance, but efficacy in brief therapy in more diverse populations, including patients with bipolar II disorder (BDII)/bipolar disorder not otherwise specified (BDNOS) with syndromal/subsyndromal depressive/mood elevation symptoms and taking/not taking concurrent medications remains to be established. METHODS: Fifty adult outpatients (24 BD1, 22 BDII, 4 BDNOS, mean ± SD age 40.8 ± 11.5 years, 28.1% female, already taking 1.1 ± 1.2 [median 1] prescription psychotropics) with 17-item Hamilton Depression Rating Scale (HDRS) ≥10 and/or Young Mania Rating Scale (YMRS) ≥10 and ≤24, were randomized to double-blind olanzapine (2.5-20 mg/day) versus placebo for one week. RESULTS: Among 45 patients with post-baseline ratings, olanzapine (9.0 ± 5.8 mg/day, n = 23) compared to placebo (n = 22) tended to yield greater Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (-1.4 ± 0.9 versus -0.8 ± 1.1, p = 0.08) and Hamilton Anxiety Scale (-7.9 ± 6.3 versus -3.8 ± 6.1, p = 0.07) improvements, and YMRS/HDRS remission rate (47.8% versus 22.7%, p = 0.08), but significantly increased median weight (+2 versus -1 lbs, p = 0.001), and rates of excessive appetite (54.2% versus 22.7%, p = 0.04) and tremor (50.0% versus 9.1% p = 0.004). Number Needed to Treat and 95% Confidence Interval for YMRS/HDRS remission were 4 (1-∞). Numbers Needed to Harm for excessive appetite and tremor were 4 (1-21) and 3 (1-6), respectively. CONCLUSIONS: Olanzapine tended to yield affective improvement and significantly increased weight, appetite, and tremor. Larger controlled studies appear feasible and warranted to assess brief olanzapine therapy in heterogeneous symptomatic bipolar disorder patients.

Effectiveness of quetiapine plus lamotrigine maintenance therapy in challenging bipolar disorder patients.

OBJECTIVE: Assess quetiapine plus lamotrigine (QTP+LTG) combination maintenance therapy effectiveness in challenging bipolar disorder (BD). METHOD: Outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form were naturalistically prescribed QTP+LTG. RESULTS: Fifty-four outpatients with challenging BD, taking in addition to QTP+LTG, a mean±SD of 2.1±1.6 (in 63.0% at least 2) other psychotropic and 2.3±1.9 non-psychotropic prescription medications, had QTP+LTG maintenance trials. Median(mean±SD) QTP+LTG duration was 401(730±756) days. Final QTP and LTG doses were 87.5(188±211) and 300(287±108) mg/day, respectively. Half (27/54) of patients discontinued QTP (in 19), LTG (in 6), or QTP+LTG (in 2), after 294(415±414) days - due to side-effects in 10, inefficacy in seven, non-adherence in five, and other reasons in five. 42.6%(23/54) had additional pharmacotherapy intervention for emergent mood symptoms, after 175(261±237) days, with at least one psychotropic added (in 16/54) or substantively (by ≥50%) increased (in 7/54). 55.6%(30/54) had recurrent mood episodes, after 126(187±158) days, most often depressive (in 35.2%), although 64.8%(35/54) were euthymic at final visit taking QTP+LTG. Sedation increased significantly during treatment among those with side-effect discontinuations, and 19.2%(10/52, all having QTP added to LTG) had clinically significant (≥7%) weight gain. LIMITATIONS: No placebo comparison group. Small sample of predominantly female Caucasian insured outpatients taking complex concurrent medication regimens. CONCLUSION: Additional studies are warranted to confirm our preliminary observation that QTP+LTG maintenance may be effective in patients with challenging BD.

Open adjunctive ziprasidone associated with weight loss in obese and overweight bipolar disorder patients.

OBJECTIVE: To assess effectiveness and tolerability of open adjunctive ziprasidone for weight loss in obese/overweight patients with bipolar disorders (BD) in diverse mood states, taking weight gain-implicated psychotropic medications. METHOD: 22 obese and three overweight BD patients (20 female; 10 BD-I, 14 BD-II, 1 BD-NOS) with mean ± SD baseline body mass index (BMI) of 31.8 ± 2.5 kg/m2 received ZIP (mean final dose 190 ± 92 mg/day) for mean of 79.2 ± 23.2 days. Weight was assessed at six weekly and three biweekly visits. Subjects entered the study in diverse mood states. At baseline, 21 were taking second-generation antipsychotics, 7 lithium, and 1 valproate, which could be reduced/discontinued at investigators' discretion. RESULTS: Weight and BMI decreased from baseline to endpoint by 4.5 ± 3.4 kg and 1.6 ± 1.2 kg/m2, respectively, at weekly rates of 0.37 kg and 0.13 kg/m2, respectively (all p < 0.00001). 48% of patients had at least 5% weight loss. Obesity rate decreased from 88% to 35% (p < 0.0001). Waist circumference decreased 1.6 inches (p = 0.0001). Overall, mood did not change. Patients with at least moderate baseline mood symptoms experienced significant mood improvement, despite 72% patients decreasing/discontinuing weight gain-implicated psychotropic medications. Seven patients discontinued ZIP early: 3 for weight loss inefficacy, and 1 each for viral gastroenteritis, loss of consciousness, pneumonia with hypomania, and lost to follow up. CONCLUSION: Open adjunctive ziprasidone may be effective for weight loss in obese/overweight BD patients taking weight gain-implicated psychotropic medications. These preliminary data should be considered with caution due to the open uncontrolled design, small sample size, and brief duration.

Toward interaction of affective and cognitive contributors to creativity in bipolar disorders: a controlled study.

BACKGROUND: Enhanced creativity in bipolar disorder patients may be related to affective and cognitive phenomena. METHODS: 32 bipolar disorder patients (BP), 21 unipolar major depressive disorder patients (MDD), 22 creative controls (CC), and 42 healthy controls (HC) (all euthymic) completed the Revised Neuroticism Extraversion Openness Personality Inventory (NEO), the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), the Myers-Briggs Type Inventory (MBTI); the Barron-Welsh Art Scale (BWAS), the Adjective Check List Creative Personality Scale, and the Figural and Verbal Torrance Tests of Creative Thinking. Mean scores were compared across groups, and relationships between temperament/personality and creativity were assessed with bivariate correlation and hierarchical multiple linear regression. RESULTS: BP and CC (but not MDD) compared to HC had higher BWAS-Total (46% and 42% higher, respectively, p<0.05) and BWAS-Dislike (83% and 93% higher, p<0.02) scores, and higher MBTI-Intuition preference type rates (78% vs. 50% and 96% vs. 50%, p<0.05). BP, MDD, and CC, compared to HC, had increased TEMPS-A-Cyclothymia scores (666%, 451% and 434% higher, respectively, p<0.0001), and NEO-Neuroticism scores (60%, 57% and 51% higher, p<0.0001). NEO-Neuroticism and TEMPS-A Cyclothymia correlated with BWAS-Dislike (and BWAS-Total), while MBTI-Intuition continuous scores and NEO-Openness correlated with BWAS-Like (and BWAS-Total). LIMITATIONS: Relatively small sample size. CONCLUSIONS: We replicate the role of cyclothymic and related temperaments in creativity, as well as that of intuitive processes. Further studies are needed to clarify relationships between creativity and affective and cognitive processes in bipolar disorder patients.

Cognitive functioning during highly active antiretroviral therapy interruption in human immunodeficiency virus type 1 infection.

Although no longer considered therapeutically beneficial, antiretroviral treatment interruptions (TIs) still occur frequently among patients with human immunodeficiency virus (HIV) infection for a variety of reasons. TIs typically result in viral rebound and worsening immunosuppression, which in turn are risk factors for neurocognitive decline and dementia. We sought to determine the extent of neurocognitive risk with TIs and subsequent reintroduction of highly active antiretroviral therapy (HAART) by using a comprehensive, sensitive neuropsychological assessment and by concurrently determining changes in plasma and cerebrospinal fluid (CSF) viral load and CD4 counts. Prospective, serial, clinical evaluations including neuropsychological (NP) testing and measurement of plasma HIV RNA and CD4 count and mood state were performed on HIV-1-infected individuals (N=11) at three time points: (1) prior to a TI, while on HAART; (2) after TIs averaging 6 months; and (3) after reinitiating HAART therapy. During TI, plasma HIV RNA increased and CD4 counts declined significantly, but NP performance did not change. Following reinitiation of HAART, viral loads fell below pre-TI levels, and CD4 counts rose. Improved viral suppression and immune restoration with reinitiation of HAART resulted in significant improvement in neurocognitive performance. No changes on comprehensive questionnaires of mood state were observed in relation to TI.NP performance and mood state remained stable during TIs despite worsened viral loads and CD4 counts. Because "practice effects" are generally greatest between the first and second NP testing sessions, improvement at the third, post-TI time point was unlikely to be accounted for by practice. TIs of up to 6 months appear to be neurocognitively and psychiatrically safe for most patients.

Pain associated with hysteroscopic sterilization.

BACKGROUND AND OBJECTIVES: The safety and efficacy of female hysteroscopic sterilization using the Essure system has been well documented. Given the marked differences in the execution of hysteroscopic and laparoscopic sterilization, the objective of this study was to assess the experience of pain postprocedure between the 2. Secondary end-points included postoperative pain medication, time to return to normal activities, postprocedure bleeding, and patient satisfaction. METHODS: Twenty cases each of laparoscopic sterilization (LS) and hysteroscopic sterilization (HS) were performed. Patients were surveyed regarding their experience of pain immediately postoperatively, 1 week, and 4 weeks postprocedure. RESULTS: The average pain score immediately postprocedure was significantly lower among HS patients than among LS patients (t=-8.17, P<.0001). One-week postprocedure, none of the patients in the HS group reported any pain, while the average pain score among the LS patients was 2.65 (t=-9.67, P<.0001). Four weeks postprocedure, women in the HS group continued to report no pain, 35% of the LS group continued to report some pain (t=-3.04, P=.004). CONCLUSIONS: Hysteroscopic sterilization offers a minimally invasive, less painful, equally efficacious modality for sterilization than laparoscopic sterilization and should be available to all women seeking permanent birth control.

A summary of reported pregnancies after hysteroscopic sterilization.

The purpose of this article is to describe 64 unintended pregnancies reported by patients who had undergone hysteroscopic sterilization and to provide recommendations for avoiding post-procedure pregnancies. Sixty-four pregnancies out of an estimated 50,000 procedures were reported to the device manufacturer from 1997 through December 2005. Most occurred in patients without appropriate follow-up. Other causes included misread hysterosalpingograms, undetected preprocedure pregnancies, and failure to follow product-labeling guidelines. The risk of pregnancy with hysteroscopic sterilization may be reduced by educating patients about the necessity of follow-up, ensuring that patients use effective contraception before and after placement, following the instructions for use, and adhering to the hysterosalpingography protocol.

Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders.

The benefits of combination antiretroviral therapy (ART) for HIV cognitive disorders vary substantially between individuals. This study evaluated whether cerebrospinal fluid (CSF) drug penetration and CSF virological suppression influence the extent of neuropsychological (NP) improvement during ART. Overall performance on a battery of NP tests administered at baseline and follow-up (median 15 weeks) was computed by using the global deficit score (GDS) methods in 31 cognitively impaired, HIV-infected individuals who began new ART regimens. Virological suppression (attaining undetectable viral load by RT-PCR at follow-up) was assessed separately for plasma and CSF. Subjects on regimens containing greater numbers of CSF-penetrating drugs showed significantly greater reduction in CSF viral load. Subjects attaining CSF virological suppression demonstrated greater GDS improvement than those who did not (median GDS change, 0.62 vs 0.23; p = 0.01). A similar trend for plasma did not reach statistical significance (p = 0.053). NP improvement was greater in ART-naive versus treatment-experienced subjects. In a multivariate model (overall p = 0.0008), significant, independent predictors of GDS reduction were CSF HIV RNA suppression, baseline antiretroviral history, and their interaction. Including CSF-penetrating drugs in the ART regimen and monitoring CSF viral load may be indicated for individuals with HIV-associated cognitive impairment.

Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy.

Abuse of methamphetamine (METH) is a frequent comorbidity among individuals infected with human immunodeficiency virus (HIV) type 1. In cell cultures and animal models, METH accelerates retroviral replication. To determine whether METH increases HIV replication in humans, we evaluated HIV loads in HIV-positive METH users and nonusers. We studied 3 groups: Tox+, active METH use and positive urine toxicology results; METH(+)Tox-, previous METH dependence/abuse and negative urine toxicology results; METH(-)Tox-, no METH dependence/abuse and negative urine toxicology results. Tox+ subjects' plasma virus loads were significantly higher than METH(+)Tox- and METH(-)Tox- subjects'; cerebrospinal fluid virus loads showed a similar but nonsignificant trend. Stratification by use of highly active antiretroviral therapy (HAART) revealed that virus loads were higher only in those Tox+ subjects who reported receiving HAART. In contrast, abstinent former METH abusers (METH(+)Tox-) receiving HAART effectively suppressed viral replication. These data suggest that abstinence programs are a key component of effective treatment of HIV in METH-abusing populations.

Human immunodeficiency virus-1 RNA levels in cerebrospinal fluid exhibit a set point in clinically stable patients not receiving antiretroviral therapy.

To characterize, over time, cerebrospinal fluid (CSF) virus-load change in clinically stable patients, human immunodeficiency virus (HIV)-1 RNA levels were measured in serial CSF samples and in plasma samples obtained, during periods of 20 days-6 years, from 17 HIV-infected individuals not receiving antiretroviral treatment. Longitudinal trends were analyzed by linear regression and restricted maximum-likelihood techniques. CSF HIV-1 RNA levels varied within a restricted range (+/-0.5 log(10) copies/mL) around each subject-specific mean. Although 16 of the 17 subjects had CSF slopes not significantly different from zero, slopes that were more positive were associated with lower CD4 counts. In an individual patient, a CSF virus-load change >0.5 log(10) copies/mL may be clinically significant. Furthermore, our data suggest that, if the CSF virus load reflects the size of the reservoir of infected cells in the central nervous system, this reservoir may increase in those individuals with advanced immunosuppression but is stable, over several years, in patients without AIDS.

Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA.

BACKGROUND: If cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA levels are elevated before the development of neuropsychological (NP) impairment, such an observation would support prospective monitoring of CSF HIV RNA levels as well as therapeutic interventions designed to lower CSF HIV levels. OBJECTIVE: To determine whether increased CSF HIV RNA levels at an earlier time predict subsequent progression to NP impairment in HIV-infected subjects. METHODS: We examined 139 subjects in a prospective cohort study. Comprehensive NP, neuromedical, and laboratory evaluations were performed at initial and follow-up visits at least 6 months apart. Human immunodeficiency virus RNA levels in plasma and CSF were measured with a commercially available, polymerase chain reaction-based assay. To assess the robustness of our findings, we analyzed changes in NP performance over time in 2 ways. First, we used masked clinical ratings of global NP performance to identify individuals who were initially NP normal, and then determined, in a similarly blinded fashion, which of these subjects subsequently became NP impaired. Second, in a separate analysis, we assessed change in subjects' raw scores on each of a series of NP test measures between baseline and follow-up. RESULTS: Among subjects who were not impaired at the initial visit, higher levels of HIV RNA in CSF significantly predicted progression to global NP impairment at the follow-up evaluation. Cerebrospinal fluid HIV RNA levels outperformed other clinical and laboratory measures in predicting progression to NP impairment. Higher CSF HIV RNA levels were associated with worsening performance on tests of attention, learning, and motor function. CONCLUSION: Because elevated CSF HIV RNA levels (>or=200 copies/mL) predict subsequent progression to NP impairment, monitoring of CSF viral load and therapy to reduce CSF HIV RNA levels may be clinically warranted, even if impairment is not identified at the time of lumbar puncture.