Regularity of self-reported daily dosage of mood stabilizers and antipsychotics in patients with bipolar disorder.

BACKGROUND: Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. METHODS: Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. RESULTS: There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). CONCLUSION: Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.

A magnetoencephalography investigation of coherence source imaging in panic disorder.

Limbic and frontal structures are largely implicated in panic disorder (PD). Decreased coherence imaging values, as determined by magnetoencephalography (MEG), are suggestive of decreased or inefficient communication among these structures. We have previously demonstrated that coherence source imaging (CSI) values could be similar or higher in some PD patients. The purpose of the current investigation was to replicate these finding in a larger sample. Nine strictly diagnosed PD patients and nine age-matched and sex-matched healthy controls were examined. The CSI-MEG values of 26 frontotemporal regions (FTRs) and 28 extra-frontotemporal regions (ex-FTR; Brodmann areas) were determined for each participant. MEG scans were acquired using a 151-channel whole-head biomagnetometer system. Despite the relatively small sample size, CSI values were significantly lower in a number of FTRs in PD patients. In none of the ex-FTRs (i.e. posterior regions) were there differences between panic and control groups. The above data add to the complexity of understanding the nature of the pathophysiology of PD. Our finding of decreased focal coherence imaging values may reflect decreased excitability in these areas. The preliminary finding could be interpreted as an inhibitory process guarding against the spread of activity in closer hyperexcitable areas as seen in epilepsy. The current data provide evidence for dysfunctional communication within the frontotemporal structures. The findings have implications for the understanding of the neural circuitry underlying PD.

Common use of dietary supplements for bipolar disorder: a naturalistic, self-reported study.

BACKGROUND: Dietary supplements are taken by about half of Americans. Knowledge of dietary supplement use is important because they may interact with prescription drugs or other supplements, cause adverse reactions including psychiatric symptoms, or contain inherently toxic ingredients or contaminants. This study explores the use of dietary supplements by patients with bipolar disorder in the US. METHODS: Data were obtained from an ongoing, naturalistic study of patients with bipolar disorder who received pharmacological treatment as usual. The patients self-reported their daily mood, sleep, and medications taken, including all drugs prescribed for bipolar disorder or that the patient felt impacted their mood. These included other prescribed drugs, over-the-counter drugs and dietary supplements. Drugs that received premarketing approval from the FDA were not included as dietary supplements. Patient demographics and daily medication use were characterized. RESULTS: Data were available from 348 patients in the US who returned a mean 249.5 days of data. In addition to prescribed psychiatric drugs, 101 of the 348 patients (29 %) used a dietary supplement for at least 7 days and 69 (20 %) used a supplement long term (for at least 50 % of days). Of the 101 supplement users, 72 (71.3 %) took one supplement daily. The 101 patients tried over 40 different supplements, and the long-term users took 19 different supplements. The most commonly taken supplements for both groups were fish oil, B vitamins, melatonin, and multivitamins. Patients using supplements were more likely to be white (p < 0.001), older (p = 0.009), and ill for more years (p = 0.025). CONCLUSIONS: Many patients with bipolar disorder use dietary supplements in addition to prescribed drugs. Physicians should obtain detailed information about all dietary supplements taken by patients with bipolar disorder.

Psychological aspects of dialysis: a case-based discussion.

End-stage renal disease is a life-threatening condition that requires the assessment and contribution of a multifaceted treatment plan. The management of patients with kidney failure is at times very challenging and requires sudden adaptation to treat this devastating illness. The role of the professionals and the dialysis unit itself will be of invaluable help in assisting the adaptation to the disease that has impacted the life of the individual in so many spheres.

Drug treatment patterns in bipolar disorder: analysis of long-term self-reported data.

BACKGROUND: The objective of this study is to investigate drug treatment patterns in bipolar disorder using daily data from patients who received treatment as usual. METHODS: Patients self-reported the drugs taken daily for about 6 months. Daily drug use and drug combinations were determined for each patient, both by the specific drugs and by medication class. The drug load was calculated for all drugs taken within a medication class. RESULTS AND DISCUSSION: Four hundred fifty patients returned a total of 99,895 days of data (mean 222.0 days). The most frequently taken drugs were mood stabilizers. Of the 450 patients, 353 (78.4%) took a stable drug combination for ≥50% of days. The majority of patients were taking polypharmacy, including 75% of those with a stable combination. Only a small number of drugs were commonly taken within each medication class, but there were a large number of unique drug combinations: 52 by medication class and 231 by specific drugs. Eighty percent of patients with a stable combination were taking three or less drugs daily. Patients without a stable combination took drugs but made frequent changes. Taking more than one drug within a medication class greatly increased the drug load. To summarize, (1) patients were more likely to take a mood stabilizer than any other drug; (2) although most patients were taking polypharmacy, there were no predominant drug regimens even among those taking a stable combination; and (3) most patients with a stable combination take a relatively small number of drugs daily. The wide variation in drug regimens and numerous possible drug combinations suggest that more evidence is needed to optimize treatment of bipolar disorder.

Antidepressant dosage taken by patients with bipolar disorder: factors associated with irregularity.

BACKGROUND: This study analyzed regularity in the daily dosage of antidepressants taken by patients with bipolar disorder and identified the factors associated with irregularity. METHODS: Daily self-reported medication dosage taken and mood ratings were available from 144 patients who received treatment as usual. All 144 patients took the same antidepressant for at least 100 days. One hundred eleven of these patients were also taking a mood stabilizer. Approximate entropy (ApEn) was used to measure serial regularity in daily dosage. Regularity is the tendency that values within a time series remain the same on incremental comparisons. Drug holidays (missing three or more consecutive days) were also determined. Generalized estimating equations (GEE) were used to estimate if any demographic or clinical variables were associated with regularity. RESULTS: Although the mean percent of days missing doses was only 18.6%, there was a wide range of regularity in the daily antidepressant dosage. Drug holidays were common, occurring in 41% of the analyses. Factors significantly associated with irregularity were as follows: total number of psychotropic medications (p = 0.005), pill burden (p = 0.005), and depression (p = 0.015). Neither the percent of days missing doses nor the drug holidays were associated with any demographic or clinical factors. For patients taking both antidepressants and mood stabilizers, there was no significant difference in regularity in daily dosage between these drugs. DISCUSSION: There can be considerable irregularity in daily dosage despite a low percent of days missing doses. Medication regimen complexity and depressed mood are associated with increased irregularity. Daily regularity in drug dosage may be more dependent on the individual than on the specific drug. Research on the clinical impact of irregularity in daily dosage of antidepressants is needed.

Brief depressive symptoms in patients with bipolar disorder: analysis of long-term self-reported data.

OBJECTIVE: Most patients with bipolar disorder experience depressive symptoms outside of an episode of depression as defined by DSM-IV criteria. This study explores the frequency of brief depressive episodes, lasting 1 to 4 days, using daily self-reported mood ratings. METHOD: Mood ratings were obtained from 448 patients (281 bipolar I, 167 bipolar II) using ChronoRecord software (91,786 total days). Episodes of depression and days of depression outside of episodes were determined. The intensity of depressive symptoms (mild versus moderate to severe) was compared. RESULTS: Using the DSM-IV length criteria, 61% of all depressive days occurred outside of a depressed episode. Decreasing the minimum length criterion to 2 days, both the number of patients experiencing a depressed episode (128 to 317) and the mean percent of days spent in a depressed episode by each patient (7.9% to 17.8.%) increased by about 2½ times, and 34.3% of depressed days remained outside of an episode. Depending on the episode length, the proportion of days within an episode with severe symptoms varied from 1/3 to 1/4 for episodes lasting from 14 to 2 days, and 1/4 for single-day episodes. There was no significant difference in the frequency of brief depressive episodes between bipolar I and II disorders. For all episode lengths, patients taking antidepressants spent 4% more days within an episode and 6% more days with depressive symptoms outside of an episode than those not taking antidepressants. CONCLUSION: Brief depressive episodes lasting 1 to 4 days occur frequently in bipolar disorder and do not distinguish between bipolar I and II disorders. Symptoms of moderate to severe intensity occur on 1/4 to 1/3 of the days in brief depressive episodes. This study did not address brief depression in those without bipolar disorder. Patients taking antidepressants experienced more brief depressive episodes. Controlled trials are needed to assess the impact of antidepressants on subsyndromal depressive symptoms.

Impact of sunlight on the age of onset of bipolar disorder.

OBJECTIVE: Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. METHOD: Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. RESULTS: The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= -4.724, 95% CI: -8.124 to -1.323, p=0.006), controlling for each country's median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. CONCLUSION: The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.

Decreasing the minimum length criterion for an episode of hypomania: evaluation using self-reported data from patients with bipolar disorder.

Brief hypomania lasting less than 4 days may impair functioning and help to detect bipolarity. This study analyzed brief hypomania that occurred in patients with bipolar disorder who were diagnosed according to the DSM-IV criteria. Daily self-reported mood ratings were obtained from 393 patients (247 bipolar I and 146 bipolar II) for 6 months (75,284 days of data, mean 191.6 days). Episodes of hypomania were calculated using a 4, 3, 2, and single day length criterion. Brief hypomania occurred frequently. With a decrease in the minimum criterion from 4 days to 2 days, there were almost twice as many patients with an episode of hypomania (102 vs. 190), and more than twice as many episodes (305 vs. 863). Single days of hypomania were experienced by 271 (69%) of the sample. With a 2-day episode length, 33% of all hypomania remained outside of an episode. There was no significant difference in the percent of hypomanic days outside of an episode between patients with bipolar I and II disorders. There were no significant differences in the demographic characteristics of patients who met the 4-day minimum as compared with those who only experienced episodes of hypomania using a shortened length criterion. Decreasing the minimum length criterion for an episode of hypomania will cause a large increase in the number of patients who experience an episode and in the aggregate number of episodes, but will not distinguish subgroups within a sample who meet the DSM-IV criteria for bipolar disorder. Frequency may be an important dimensional aspect of brief hypomania. Clinicians should regularly probe for brief hypomania.

Association between median family income and self-reported mood symptoms in bipolar disorder.

OBJECTIVE: There is broad consensus from epidemiologic research that lower socioeconomic status is related to poorer health. This study investigated the relation between median family income and self-reported mood symptoms in patients with bipolar disorder who reside in the United States. METHODS: Two hundred eighty-four patients with bipolar disorder provided daily self-reported mood ratings for 6 months (50,054 days of data). Regardless of income, all patients were treated by a psychiatrist, took psychotropic medications, and participated in computerized self-monitoring throughout the study. Median family income was obtained from US census tract data. The association between income and mood was analyzed using income as both a continuous and categorical variable. Demographic characteristics were compared by income group. Education level was included in the analysis a priori. RESULTS: Both the continuous and categorical approaches found a positive association between income and euthymia, a negative association between income and manic/hypomanic symptoms including those due to mixed states, and no association between income and depressive symptoms. Patients in the lower-income group spent 12.4% fewer days euthymic than those in the upper-income group and 9.7% fewer days euthymic than those in the middle-income group. Patients in the lower-income group spent 7.1% more days with manic/hypomanic symptoms than those in the upper-income group. There was no association between education and income. CONCLUSION: Median family income is associated with mood symptoms in patients with bipolar disorder. Inclusion of income as a measure of socioeconomic status is recommended for future studies of outcome in bipolar disorder.

Association between age of onset and mood in bipolar disorder: comparison of subgroups identified by cluster analysis and clinical observation.

BACKGROUND: This study compared subgroups identified by cluster analysis and clinical observation by evaluating the association between the age of onset of bipolar disorder and self-reported daily mood ratings. METHODS: Two hundred and seventy patients with bipolar disorder provided daily self-reported mood ratings for about 6 months returning 55,188 days of data. The age of onset subgroups were determined both using previously defined cutoff values based upon clinical observation (≤12 years, 13-19 years, 20-29 years, >29 years), and model-based cluster analysis. Demographic characteristics were compared in the age of onset subgroups. Univariate general linear models with age of onset subgroups and other demographic variables as fixed factors and covariates were used to analyze the percent of days depressed, euthymic and hypomanic/manic. RESULTS: Using the predetermined subgroups, demographic differences were found between the four subgroups in the diagnosis of bipolar I/II, years of illness, age and use of lamotrigine. Post-hoc pairwise comparison found that patients with an age of onset less ≤ 12 years spent more days hypomanic/manic: 16.4 percent versus 8.0 for patients with an age of onset between 13 and 19 years (p=0.006) and 8.2 percent for patients with an age of onset between 20 and 29 years (p = 0.031). The majority of the additional days of hypomania/mania occurred outside of an episode. Model-based cluster analysis found a mixture of 2 distributions of onset with peaks at age 15.1 years (SD = 4.7) and 27.5 years (SD = 10.2). Analysis of these two subgroups detected no significant differences in demographic characteristics or mood ratings. CONCLUSION: Age of onset subgroups arising from clinical observation may be more useful than those determined by cluster analysis.

The association between concurrent psychotropic medications and self-reported adherence with taking a mood stabilizer in bipolar disorder.

OBJECTIVE: Multiple psychotropic medications are routinely prescribed to treat bipolar disorder, creating complex medication regimens. This study investigated whether the daily number of psychotropic medications or the daily number of pills were associated with self-reported adherence with taking a mood stabilizer. METHODS: Patients self-reported their mood and medications taken daily for about 6 months. Adherence was defined as taking at least one pill of any mood stabilizer daily. Univariate general linear models (GLMs) were used to estimate if adherence was associated with the number of daily medications and the number of pills, controlling for age. The association between mean daily dosage of mood stabilizer and adherence was also estimated using a GLM. RESULTS: Three hundred and twelve patients (mean age 38.4 +/- 10.9 years) returned 58,106 days of data and took a mean of 3.1 +/- 1.6 psychotropic medications daily (7.0 +/- 4.2 pills). No significant association was found between either the daily number of medications or the daily number of pills and adherence. For most mood stabilizers, patients with lower adherence took a significantly smaller mean daily dosage. CONCLUSIONS: The number of concurrent psychotropic medications may not be associated with adherence in bipolar disorder. Patients with lower adherence may be taking smaller dosages of mood stabilizers.

Comparison of sleep/wake parameters for self-monitoring bipolar disorder.

BACKGROUND: Psychosocial interventions may teach patients with bipolar disorder to successfully detect warning signs of relapse. These interventions often include ongoing self-monitoring of sleep. We previously reported that a change in sleep duration (sleep plus bedrest) of >3 h may indicate that a mood change is imminent. This analysis further investigated whether sleep duration, sleep onset or sleep offset was the most useful sleep/wake parameter to monitor for an oncoming mood change. METHODS: 101 adult outpatients receiving treatment as usual recorded mood, sleep and medications every day on a home computer for a mean of 265+/-103 days. A daily time series of mood, sleep duration (sleep plus bedrest), sleep onset and sleep offset was constructed for each patient. After applying an ARIMA (0,1,1) filter, a cross correlation function was used to analyze the temporal relationship between the residuals for lags of +/-7 days. RESULTS: Less frequent significant correlations were found between a change in either sleep onset or sleep offset and mood, than between sleep duration and mood. Patients with a significant correlation between sleep duration and mood included 86% of those with a significant correlation between sleep onset or sleep offset and mood. Mean sleep duration when euthymic was long (> or =8 h in 89% of patients, > or =9 h in 51% of patients). LIMITATIONS: Self-reported data, naturalistic study, and computer access required. CONCLUSIONS: Self-monitoring of sleep duration is recommended for patients with bipolar disorder. Better understanding of the long sleep duration of euthymic patients is required.

Relationship among latitude, climate, season and self-reported mood in bipolar disorder.

OBJECTIVE: Many researchers have analyzed seasonal variation in hospital admissions for bipolar disorder with inconsistent results. We investigated if a seasonal pattern was present in daily self-reported daily mood ratings from patients living in five climate zones in the northern and southern hemispheres. We also investigated the influence of latitude and seasonal climate variables on mood. METHOD: 360 patients who were receiving treatment as usual recorded mood daily (59,422 total days of data). Both the percentage of days depressed and hypomanic/manic, and the episodes of depression and mania were determined. The observations were provided by patients from different geographic locations in North and South America, Europe and Australia. These data were analyzed for seasonality by climate zone using both a sinusoidal regression and the Gini index. Additionally, the influence of latitude and climate variables on mood was estimated using generalized linear models for each season and month. RESULTS: No seasonality was found in any climate zone by either method. In spite of vastly different weather, neither latitude nor climate variables were associated with mood by season or month. CONCLUSION: Daily self-reported mood ratings of most patients with bipolar disorder did not show a seasonal pattern. Neither climate nor latitude has a primary influence on the daily mood changes of most patients receiving medication for bipolar disorder.

Frequency of subsyndromal symptoms and employment status in patients with bipolar disorder.

OBJECTIVE: This study investigated the frequency of episodes and subsyndromal symptoms based on employment status in patients with bipolar disorder. METHODS: Patients with bipolar disorder (n = 281) provided daily self-reported mood ratings for 5 months, returning 46,292 days of data. Data were analyzed using three employment status groups: disabled (n = 75), full-time employee or full-time student (n = 135), and other (n = 71). Demographic characteristics were compared by employment status. A univariate general linear model with employment status and other demographic variables as fixed factors and covariates was used to analyze the percent of days in episodes and percent of days with subsyndromal symptoms. RESULTS: While there was no significant difference in the percent of days in episodes among the employment groups, disabled patients suffered subsyndromal symptoms of depression twice as frequently as those in the full-time group. Disabled patients spent 15% more days either in episodes or with subsyndromal symptoms than those in the full-time group, equivalent to about 45 extra sick days a year. CONCLUSION: Frequent subsyndromal symptoms, especially depressive, may preclude full-time responsibilities outside the home and contribute to disability in bipolar disorder. Additional treatments to reduce the frequency of subsyndromal symptoms are needed.

Relationship between adjunctive medications for anxiety and time spent ill in patients with bipolar disorder.

Objective. Many patients with bipolar disorder take adjunctive medications for anxiety. Using naturalistic data, we investigated the relationship between the use of adjunctive anxiolytics and the time spent in episodes or with subsyndromal mood symptoms. Methods. This was a post-hoc analysis of 310 patients with bipolar disorder who previously recorded mood and medications daily for 5 months using ChronoRecord software. One hundred patients were taking adjunctive anxiolytics for at least 50% of days; 210 were not. Of the 100 patients, 73 were taking a benzodiazepine. All patients taking anxiolytics were also receiving treatments for bipolar disorder. Results. Patients with bipolar disorder who were taking adjunctive medications for anxiety spent more time ill. Comparing patients who were taking or not taking anxiolytics, the mean days spent either in any episode or with subsyndromal symptoms was 45.6 vs. 29.6%, respectively (P<0.001), the mean days in any episode was 17.1 vs. 9.2%, respectively (P=0.016), and the mean days with subsyndromal depression was 26.4 vs. 16.2%, respectively (P=0.004). Conclusion. While this methodology cannot determine causality, these findings highlight the need for controlled studies of the long-term impact of adjunctive medications for anxiety on mood symptoms in patients being treated for bipolar disorder.

A cross-over, post-electroconvulsive therapy comparison of clinical recovery from rocuronium versus succinylcholine.

STUDY OBJECTIVE: To evaluate the effect of the neuromuscular blocking agent, rocuronium, on clinical recovery from electroconvulsive therapy (ECT) as compared with succinylcholine. DESIGN: Cross-over study. SETTING: University hospital. PATIENTS: 13 ASA physical status I and II patients, ages 18 to 60 years, receiving ECT three times a week. INTERVENTIONS: Each patient received either succinylcholine before the first ECT session (Group S) and rocuronium before the third ECT session (Group R). Muscle paralysis was produced with succinylcholine one mg kg(-1) intravenously (IV) or rocuronium 0.3 mg kg(-1) IV. Reversal of the residual neuromuscular block (Group R) was accomplished with 10 microg kg(-1)of atropine and 20 microg kg(-1)of neostigmine after completion of the ECT procedure. MEASUREMENTS: Motor seizure duration time, time to first spontaneous breathing, eye opening, head lift, and tongue depressor test were recorded. MAIN RESULT: Motor seizure duration and time to first spontaneous breath was longer (33.6 sec vs. 24.2 sec; 9.46 min vs 8.07 min, respectively) in the rocuronium group than the succinylcholine group. No significant difference was detected between the two groups in eye opening, head lift, or tongue depressor testing. CONCLUSION: Rocuronium, when used in conjunction with a reversal agent, may be an adequate alternative to succinylcholine as a neuromuscular blocker during ECT.

Toward a better identification and treatment of schizophrenia prodrome.

The prodromal period leading to schizophrenia has been the focus of significant interest in recent years. This is due not only to the possibility of identification of preschizophrenic states but also to the potential for improving prognosis as a result of early intervention. There are many approaches to the identification of the schizophrenia prodrome. Interventions in the prodromal period have met with various degrees of success. In this article, the authors present an overview of the literature reflecting the development of the prodromal concept and its implications for early identification. They also discuss various interventions proposed for this period and some ethical considerations related to these interventions. Despite the growing body of knowledge in this field, there is a need for more research data to support the establishment of treatment guidelines. Future directions of research are also discussed.

Antidepressant-associated chronic irritable dysphoria (ACID) in STEP-BD patients.

BACKGROUND: It has been proposed that antidepressants can induce a chronic, dysphoric, irritable state in bipolar patients (called ACID for antidepressant-associated chronic irritable dysphoria). This phenomenon has only been described in case series format, and has not been prospectively validated. METHODS: Prospective data from the first 1500 patients (62.7% with bipolar I, 30.1% with bipolar II, and 7.2% with NOS) treated in the STEP-BD database were examined and those who were euthymic for at least one month at study entry, subsequently developed a depressive episode, and were then followed for one year were identified. Outcome of those who received an antidepressant for this depressive episode (n=27) was compared to those who did not (n=56), with particular attention given to the presence of the proposed symptom triad of ACID, namely dysphoria, irritability, and middle insomnia. RESULTS: Patients treated with antidepressants were ten times more likely to develop ACID than those who were not (Hazard ratio=9.95, CI=1.103-89.717, P=0.04). However, the hazard ratio dropped to 1.05 (P=0.99) when corrected for significant covariates, notably past antidepressant-related manic switch and sex. DISCUSSION: This study does not support the existence of ACID as an independent phenomenon. Rather, ACID appears to be part of a broader spectrum of antidepressant treatment-emergent affective switches.