Prodromal symptoms to relapse in bipolar disorder

In a cyclical and recurring illness such as bipolar disorder, prodrome detection is of vital importance. This paper describes manic and depressive prodromal symptoms to relapse, methods used in their detection, problems inherent in their assessment, and patients' coping strategies. A review of the literature on the issue was performed using MEDLINE and EMBASE databases (1965-May 2006). 'Bipolar disorder', 'prodromes', 'early symptoms', 'coping', 'manic' and 'depression' were entered as key words. A hand search was conducted simultaneously and the references of the articles found were used to locate additional articles. The most common depressive prodromes are mood changes, psychomotor symptoms and increased anxiety; the most frequent manic prodromes are sleep disturbances, psychotic symptoms and mood changes. The manic prodromes also last longer. Certain psychological interventions, both at the individual and psychoeducational group level, have proven effective, especially in preventing manic episodes. Bipolar patients are highly capable of detecting prodromal symptoms to relapse, although they do find the depressive ones harder to identify. Learning detection, coping strategies and idiosyncratic prodromes are elements that should be incorporated into daily clinical practice with bipolar patients.     

Duration and symptoms of bipolar prodromes

The duration and symptoms of manic and depressive prodromes of 20 bipolar patients showed much interindividual variation. However, these features were consistent in successive episodes of the same type in the same patient. Manic prodromes were longer than depressive prodromes.     

Functional impairment in the remission phase of bipolar disorder

OBJECTIVES: The purpose of this study was to evaluate functional impairment in a group of patients with bipolar disorder in remission and to determine the extent of relationships between overall functioning and current depressive, manic and panic spectrum symptoms. METHOD: A subset of the patient population at the Pittsburgh site of the Systematic Treatment Enhancement Program in Bipolar Disorder (STEP-BD) study was evaluated in this study. The subsample comprises 103 male and female subjects with bipolar I disorder (n = 70), bipolar II disorder (n = 24), schizoaffective disorder - bipolar type (n = 4), or bipolar disorder NOS (n = 5). Subjects were evaluated in a period of remission (at least 4 weeks with no more than two depressive or manic symptoms). Subjects were assessed for overall functional status using the Work and Social Adjustment Scale (WSAS) and for current bipolar and panic spectrum symptoms using the Mood Spectrum Self-Report questionnaire (MOODS-SR) and Panic-Agoraphobic Spectrum Self-Report questionnaire (PAS-SR). RESULTS: The median WSAS total score in these remitted subjects was 14, indicating significant functional impairment. Regressing WSAS on current depressive, manic, and panic spectrum total scores, we observed a highly significant depressive spectrum effect (t = 4.9, df = 94, p < 0.0001), but non-significant panic and manic spectrum effects (t = 1.3, df = 94, p = 0.19 and t = -1.8, df = 94, p = 0.07, respectively). CONCLUSION: Bipolar disorder is associated with functional deficits even during periods of sustained and substantial remission. The degree of functional impairment is correlated with the degree of depressive spectrum symptoms.     

Neurobiological findings in a patient with 48-hour rapid cycling bipolar affective disorder. A case report

Forty-eight-hour rapid cycling is a rare subclass of affective disorders and entails a regular periodic change of moods. The following case study describes the symptoms, therapy, and outcome of a patient suffering from daily switching between mania and depression along with neurobiological findings correlated to the affective cycles. We found alternating reduction and prolongation of sleep duration during manic and depressive days as well as differences in the amount of REM sleep. Cortisol secretion was regularly increased during depressive days. Regarding thyroid-stimulating hormone (TSH) secretion, the circadian rhythm was absent on depressive days. However, the glucose metabolic rate as measured by positron emission tomography (PET) did not differ on manic and depressive days. The patient reached almost complete remission under treatment with lithium.     

Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up

OBJECTIVE: While guidelines for treating patients with bipolar depression recommend discontinuing antidepressants within 6 months after remission, few studies have assessed the implications of this strategy on the risk for depressive relapse. This study examined the effect of antidepressant discontinuation or continuation on depressive relapse risk among bipolar subjects successfully treated for an acute depressive episode. METHOD: Eighty-four subjects with bipolar disorder who achieved remission from a depressive episode with the addition of an antidepressant to an ongoing mood stabilizer regimen were followed prospectively for 1 year. The risk of depressive relapse among 43 subjects who stopped antidepressant treatment within 6 months after remission ("discontinuation group") was compared with the risk among 41 subjects who continued taking antidepressants beyond 6 months ("continuation group"). RESULTS: A Cox proportional hazards regression analysis indicated that shorter antidepressant exposure time following successful treatment was associated with a significantly shorter time to depressive relapse. Furthermore, patients who discontinued antidepressant treatment within the first 6 months after remission experienced a significantly shorter period of euthymia before depressive relapse over the length of 1-year follow-up. One year after successful antidepressant response, 70% of the antidepressant discontinuation group experienced a depressive relapse compared with 36% of the continuation group. By the 1-year follow-up evaluation, 15 (18%) of the 84 subjects had experienced a manic relapse; only six of these subjects were taking an antidepressant at the time of manic relapse. CONCLUSIONS: The risk of depressive relapse in patients with bipolar illness was significantly associated with discontinuing antidepressants soon after remission. The risk of manic relapse was not significantly associated with continuing use of antidepressant medication and, overall, was substantially less than the risk of depressive relapse. Maintenance of antidepressant treatment in combination with a mood stabilizer may be warranted in some patients with bipolar disorder.     

Impact of depressive symptoms compared with manic symptoms in bipolar disorder: results of a U.S. community-based sample

OBJECTIVE: In the present study, we assessed the functional impact of depressive versus manic symptoms in bipolar disorder. METHOD: A survey comprising the Sheehan Disability Scale (SDS), the Social Adjustment Scale Self-Report (SAS-SR), the Mood Disorder Questionnaire (MDQ), and other questions was mailed to a representative subset of 4810 individuals (with or without bipolar disorder) from a U.S. population-based epidemiologic study conducted in 2001. RESULTS: Of the 3191 evaluable surveys returned, 593 respondents screened positive for bipolar disorder on the MDQ and/or reported a physician diagnosis of bipolar disorder. In the 4 weeks prior to the survey, subjects reported a mean of 12.4 days of depressive symptoms and 7.0 days of manic symptoms (p < .0001). The majority of days with depressive (79.8%) and manic (77.1%) symptoms were disruptive. Both total and mean scores on each domain of the SDS (work, social life, family life) reflect significantly greater impairment because of depressive versus manic symptoms during the 4 weeks prior to the survey (p < .0001). Among the 118 employed subjects who missed at least 1 day of work in the past month, more workdays were missed because of depressive versus manic symptoms (0.78 vs. 0.15, p < .004). For each domain of the SAS-SR, functional impairment was attributed significantly more often to depressive symptoms than manic symptoms (p < .0001). Similar results were observed for the 12 months preceding the survey. CONCLUSIONS: Self-reported depressive symptoms are more frequent than manic symptoms and cause greater disruption of occupational, family, and social functioning. These findings underscore the need to improve the recognition and management of bipolar depression.     

Periodic motor impairments in a case of 48-hour bipolar ultrarapid cycling before and under treatment with valproate

Motor impairments of psychiatric patients can be assessed with digital recordings of handwriting tasks. The investigation of patients with bipolar affective disorders differentiates intraindividual changes related to the patient's fluctuating affective states. An unmedicated 67-year-old male with 48-hour bipolar ultrarapid cycling was investigated during 8 consecutive days of ultrarapid cycling and 4 weeks later, after remission under treatment with valproate. The handwriting skills of the patient followed the same rhythmic changes of the psychopathology in the first part of the study and a steady pattern in the second phase, after remission. Therefore, it can be assumed that the handwriting skills reflect a state marker of the disease. Poorer handwriting skills on the manic days, as compared to the depressive ones, support the hypothesis of a low arousal in manic patients.     

Low-dose (0.5 mg) DST in manic and major depressive episodes: in relation to the severity of symptoms]

BACKGROUND: Results of previous studies and our own preliminary study suggest that the dexamethasone suppression test (DST) using 1 mg of dexamethasone might result in lower sensitivity in Japanese and Asian people with major depressive episodes, when compared to Caucasian people. We investigated the clinical utility of low-dose (0.5 mg) DST in Japanese patients with manic or major depressive episodes. METHODS: Low-dose (0.5 mg) DST was performed 276 times in 122 patients with bipolar disorder (manic or depressed) or major depressive disorder who visited the Department of Psychiatry of Osaka Prefectural General Hospital. After strict exclusion criteria were applied, the remaining 225 test results in 98 patients were analyzed. The severity of symptoms was estimated in accordance with the DSM-IV, namely, severe, moderate, mild, or in remission. A 0.5 mg dose of dexamethasone was administered orally at 20:30, and blood samples were taken the following day at 8:00 (9:00 in outpatients) and 13:00. Serum cortisol levels were measured by radioimmunoassay. Nonsuppression was considered to have occurred when at least one of the postdexamethasone cortisol values was 4.0 micrograms/dl or over. RESULTS: In manic episodes, the postdexamethasone cortisol levels were significantly correlated with the severity of the symptoms, and the postdexamethasone cortisol levels in patients with severe symptoms were significantly higher than in those in remission. The rates of nonsuppression in manic episodes with severe, moderate, mild symptoms, and in remission, were 7/8 (88%), 1/4 (25%), 1/3 (33%) and 2/7 (29%), respectively. In major depressive episodes, the postdexamethasone cortisol levels were significantly correlated with the severity of the symptoms. The rates of nonsuppression in major depressive episodes with each grading of severity were 47/58 (81%), 28/52 (54%), 14/40 (35%), 10/53 (19%), respectively. In major depressive episodes, patients aged 50 or over showed significantly higher postdexamethasone cortisol levels than patients aged under 50. In particular, patients aged between 30 and 49 showed significantly lower postdexamethasone cortisol levels than those in the other age groups. There was no significant difference between male and female patients (two-way ANOVA), but female patients with severe depressive symptoms showed significantly higher postdexamethasone cortisol levels than male patients with severe symptoms. There was no significant difference between bipolar and unipolar patients with major depressive episodes (two-way ANOVA), with the exception that the rate of nonsuppression in remission in bipolar patients was significantly different than that in unipolar patients (9/33 (27%), 1/20 (5%), respectively). Among major depressive disorders, the rate of nonsuppression was highest in those with psychotic features, followed by those with melancholia, and then by those without melancholia. Re-evaluating the cut-off point discriminating nonsuppression from suppression, it was suggested that the optimal cut-off point might differ according to age and gender, but a fixed cut-off point at 4.0 micrograms/dl was considered to be appropriate. The postdexamethasone cortisol levels of samples obtained at 13:00 were more sensitive than those obtained at 8:00 or 9:00. The exclusion criteria and the clinical meanings of DST were discussed. CONCLUSIONS: Along with the previous studies indicating a low rate of nonsuppression in Japanese and other Asians using a standard 1 mg DST, our results suggest that low-dose (0.5 mg) DST is better in Japanese, and probably in most Asian patients, than 1 mg DST.     

Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

OBJECTIVE: Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines. The authors looked for the features associated with risk of recurrence. METHOD: The authors examined prospective data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study for up to 24 months. For those who were symptomatic at study entry but subsequently achieved recovery, time to recurrence of mania, hypomania, mixed state, or a depressive episode was examined with Cox regression. RESULTS: Of 1,469 participants symptomatic at study entry, 858 (58.4%) subsequently achieved recovery. During up to 2 years of follow-up, 416 (48.5%) of these individuals experienced recurrences, with more than twice as many developing depressive episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes (118, 13.8%). The time until 25% of the individuals experienced a depressive episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence. Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic, hypomanic, or mixed episode recurrence. CONCLUSIONS: Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery. Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence.     

Emotional hyper-reactivity as a fundamental mood characteristic of manic and mixed states.

BACKGROUND: The relationship between depression and mania remains poorly understood and is responsible for much of the confusion about mixed states. The difficulty in conceptualizing opposite states such as euphoric and depressive moods during the same episode may account for the considerable differences in reported frequencies of mixed states, among acutely manic patients. It is possible that the fundamental mood characteristic of mania is not tonality of mood (e.g. euphoric, irritable or depressed mood), but rather the intensity of emotions. METHOD: We interviewed 30 patients hospitalized for a manic episode, asking about their symptoms during the episode, using the list of symptoms for manic and depressive episode of the DSM-IV criteria. Emotional hyper-reactivity, defined as an increase in the intensity of all emotions, was assessed using the Hardy Scale. Manic symptoms were also assessed by a clinician using the Beck-Rafaelsen Mania Scale. RESULTS: This study showed that most of the manic episodes presented many dysphoric symptoms, more particularly depressive mood (33%), irritability (53%), anxiety (76%), and recurrent thoughts of death or suicidal ideation (33%). However, only 10% of our sample met the criteria for mixed state. The other symptoms reported by patients and included in the DSM-IV criteria for depressive mood are common between depressive and manic episodes. All patients (100%) reported that they felt all their emotions with an unusual intensity. CONCLUSION: We suggest that the most appropriate way to define mood in manic states is as a function of intensity, and not as a function of tonality. This definition circumvents the arbitrary dichotomy between mania and mixed state. With this definition, manic episodes can be described as being more or less dysphoric, with the actual characteristics of dysphoria encompassing irritability, anxiety, or depressive affect. This point could be extremely helpful in discriminating mixed state or dysphoric mania from depression.     

Differentiation in the preonset phases of schizophrenia and mood disorders: evidence in support of a bipolar mania prodrome

OBJECTIVE: The presence and specificity of a bipolar prodrome remains questioned. We aimed to characterize the prodrome prior to a first psychotic and nonpsychotic mania and to examine the phenotypic proximity to the schizophrenia prodrome. METHODS: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective, information regarding the mania prodrome was collected from youth with a research diagnosis of bipolar I disorder and onset before 19 years of age, and/or their caregivers. Only newly emerging, at least moderately severe, symptoms were analyzed. Prodromal characteristics were compared between patients with and without subsequent psychotic mania and with published bipolar and schizophrenia prodrome data. RESULTS: In 52 youth (age at first mania: 13.4 +/- 3.3 years), the prodrome onset was predominantly "insidious" (>1 year, 51.9%) or "subacute" (1-12 months, 44.2%), while "acute" presentations (<1 month, 3.8%) were rare. The prodrome duration was similar in patients with (1.7 +/- 1.8 years, n = 34) and without (1.9 +/- 1.5 years, n = 18) subsequent psychotic mania (P = .70). Attenuated positive symptoms emerging late in the prodrome and increased energy/goal-directed activity were significantly more common in patients with later psychotic mania. Mania and schizophrenia prodrome characteristics overlapped considerably. However, subsyndromal unusual ideas were significantly more likely part of the schizophrenia prodrome, while obsessions/compulsions, suicidality, difficulty thinking/communicating clearly, depressed mood, decreased concentration/memory, tiredness/lack of energy, mood lability, and physical agitation were more likely part of the mania prodrome. CONCLUSIONS: A lengthy and symptomatic prodrome makes clinical high-risk research a feasible goal for bipolar disorder. The phenotypic overlap with the schizophrenia prodrome necessitates the concurrent study of both illness prodromes.     

Are prodromes preictal events? A prospective PDA-based study

Up to 29% of patients with epilepsy report "prodromal" sensations more than 30 minutes prior to seizures. We developed and implemented an objective methodology to prospectively assess the sensitivity and specificity of these subjective experiences using personal digital assistants (PDAs). The key property, in contrast to paper-based diaries, is the internal recording of the patient's entering time of prodromes and seizures. Of 500 patients with epilepsy interviewed, 31 claimed to sense prodromal symptoms at least 30 minutes before seizure onset. Eleven of them agreed to participate in a 4-week study to objectively measure their prospective prediction performance. In 9 patients returning data, the majority of prodrome entries were not followed by seizures or were identified only retrospectively. Statistical analysis revealed that no patient could outperform a nonspecific random predictor when predicting seizures based on the occurrence of prodromes, and that the group performance matched precisely the expected result for a by-chance prediction. These results question the predictive value of "prodromes" and the specificity of their occurrence in the preictal period.     

Olanzapine versus divalproex in the treatment of acute mania

OBJECTIVE: The effects of olanzapine and divalproex for the treatment of mania were compared in a large randomized clinical trial. METHOD: A 3-week, randomized, double-blind trial compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day in divided doses) for the treatment of patients hospitalized for acute bipolar manic or mixed episodes. The Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to quantify manic and depressive symptoms, respectively. Safety was assessed with several measures. RESULTS: The protocol defined baseline-to-endpoint improvement in the mean total score on the Young Mania Rating Scale as the primary outcome variable. The mean Young Mania Rating Scale score decreased by 13.4 for patients treated with olanzapine (N=125) and 10.4 for those treated with divalproex (N=123). A priori categorizations defined response and remission rates: 54.4% of olanzapine-treated patients responded (> or = 50% reduction in Young Mania Rating Scale score), compared to 42.3% of divalproex-treated patients; 47.2% of olanzapine-treated patients had remission of mania symptoms (endpoint Young Mania Rating Scale < or = 12), compared to 34.1% of divalproex-treated patients. The decrease in Hamilton depression scale score was similar in the two treatment groups. Completion rates for the 3-week study were similar in both groups. The most common treatment-emergent adverse events (incidence >10%) occurring more frequently during treatment with olanzapine were dry mouth, increased appetite, and somnolence. For divalproex, nausea was more frequently observed. The average weight gain with olanzapine treatment was 2.5 kg, compared to 0.9 kg with divalproex treatment. CONCLUSIONS: The olanzapine treatment group had significantly greater mean improvement of mania ratings and a significantly greater proportion of patients achieving protocol-defined remission, compared with the divalproex treatment group. Significantly more weight gain and cases of dry mouth, increased appetite, and somnolence were reported with olanzapine, while more cases of nausea were reported with divalproex.     

Health-related quality of life and functioning in remitted bipolar I outpatients

The aim of this study was to characterize the health-related quality of life (HR-QOL) and functioning in 90 bipolar I remitted outpatients. According to Diagnostic and Statistical Manual of Mental Disorders IV remission specifiers, patients were categorized into 4 groups: group 1, fully remitted; group 2, less than 2 months remitted; group 3, with persisting manic symptoms; group 4, with persisting depressive symptoms. The severity of psychopathology was evaluated by using the Bech-Rafaelsen Mania-Melancholia Scale. The HR-QOL, functioning, and insight were assessed via the medical outcomes study 36-item short form, the global assessment of functioning scale, and the scale to assess unawareness of mental disorder, respectively. Fully remitted patients reported the highest scores in almost all domains of medical outcomes study 36-item short form, and had significantly higher scores on physical functioning, general health, social functioning, and mental health compared to patients with persisting depressive symptoms. Furthermore, patients with persisting manic symptoms reported significantly higher scores on general health, vitality and mental health than the group with persisting depressive symptoms. In contrast, the global assessment of functioning scale score differed among the 4 groups, with fully remitted patients reporting higher, although not statistically significant, scores than the other groups. Our data suggest that the persistence of depressive or manic symptoms seem to affect self-report measures of HR-QOL. An affectively biased cognition may explain the gap between patient's perception of functioning and estimated functional adjustment, as assessed by clinicians.     

Manic symptoms and impulsivity during bipolar depressive episodes

OBJECTIVES: In contrast to the extensive literature on the frequent occurrence of depressive symptoms in manic patients, there is little information about manic symptoms in bipolar depressions. Impulsivity is a prominent component of the manic syndrome, so manic features during depressive syndromes may be associated with impulsivity and its consequences, including increased risk of substance abuse and suicidal behavior. Therefore, we investigated the prevalence of manic symptoms and their relationships to impulsivity and clinical characteristics in patients with bipolar depressive episodes. METHODS: In 56 bipolar I or II depressed subjects, we investigated the presence of manic symptoms, using Mania Rating Scale (MRS) scores from the Schedule for Affective Disorders and Schizophrenia (SADS), and examined its association with other psychiatric symptoms (depression, anxiety, and psychosis), age of onset, history of alcohol and/or other substance abuse and of suicidal behavior, and measures of impulsivity. RESULTS: MRS ranged from 0 to 29 (25th-75th percentile, range 4-13), and correlated significantly with anxiety and psychosis, but not with depression, suggesting the superimposition of a separate psychopathological mechanism. Impulsivity and history of substance abuse, head trauma, or suicide attempt increased with increasing MRS. Receiver-operating curve analysis showed that MRS could divide patients into two groups based on history of alcohol abuse and suicide attempt, with an inflection point corresponding to an MRS score of 6. DISCUSSION: Even modest manic symptoms during bipolar depressive episodes were associated with greater impulsivity, and with histories of alcohol abuse and suicide attempts. Manic symptoms during depressive episodes suggest the presence of a potentially dangerous combination of depression and impulsivity.     

Changes in insight among patients with bipolar I disorder: a 2-year prospective study

OBJECTIVES: The aim of this 2-year prospective study was to examine changes in insight among bipolar patients with different clinical courses. METHODS: A cohort of 65 patients with bipolar I disorder in remission was recruited for this study. They received six follow-up assessments over a 2-year period. The Schedule of Assessment of Insight-Expanded version (SAI-E) was used to determine their levels of insight, while the Young Mania Rating Scale (YMRS) and the Hamilton Rating Scale for Depression (HAM-D) were used to determine affective symptoms. Types of changes in insight among bipolar patients were analyzed according to the different clinical courses during the 2-year follow-up period. RESULTS: Insight in consistently stable patients was steady during the 2-year period. Insight decreased during the manic period in patients with only a single manic episode as well as in those with repeated manic episodes. However, insight returned to the pre-episode level for patients with only a single manic episode, but did not for most of the patients with repeated episodes. No changes in insight were observed during depressive episodes for either patients with a single or those with repeated depressive episodes. CONCLUSIONS: The types of insight changes among bipolar patients during the 2-year period were various and depended on the different clinical courses. Frequent mood disturbance episodes may cause patient insight to deteriorate.     

Vulnerability to psychosis in patients attending primary and psychiatric care. Results of the RADEP study

We studied occurrence of psychotic symptoms and their associations with occurrence of depressive and manic symptoms; 563 patients attending primary care (PrC) and 163 patients attending psychiatric outpatient care (PsC) completed a questionnaire including lists of psychotic, manic and depressive symptoms, and patients with depressive symptoms were interviewed using the same questionnaire 6 months after baseline examination. Of PrC patients, 8.5% and of PsC patients, 36.2% reported at least seven lifetime psychotic symptoms. During the 6-month follow-up, the corresponding figures were 0.22% for PrC and 2.84% for PsC patients. Among PrC patients, men, young, never-married, students and unemployed reported more psychotic symptoms than others. In multivariate analyses, occurrence of psychotic symptoms was associated with young age, never being married, poor functioning and former psychiatric treatment, as well as with occurrence of manic and depressive symptoms. Psychotic symptoms are rather prevalent in primary care and very common in psychiatric care. In primary care, vulnerability to psychosis is associated with the patient's background more strongly than in psychiatric care. Concurrent occurrence of psychotic symptoms with manic and depressive symptoms is common.     

Agitated "unipolar" major depression: prevalence, phenomenology, and outcome

OBJECTIVE: This study aimed to explore how prevalent agitated "unipolar" major depression is, whether it belongs to the bipolar spectrum, and whether it differs from nonagitated "unipolar" major depression with respect to course and outcome. METHOD: The study was conducted from January 1, 1978, to December 31, 1996. From 361 patients with major depressive disorder, the authors selected those fulfilling Research Diagnostic Criteria for agitated depression. These 94 patients were compared to 94 randomly recruited patients with nonagitated major depressive disorder regarding demographic and historical features, the clinical characteristics of the index episode, the percentage of time spent in an affective episode during a prospective observation period, and the 5-year outcome. Patients with agitated major depressive disorder who had at least 2 manic/hypomanic symptoms in their index episode were compared to the other patients with agitated major depressive disorder with respect to the same variables. RESULTS: Patients with agitated major depressive disorder were more likely to receive antipsychotics during their index episode and spent a higher proportion of time in an affective episode during the observation period compared with patients with nonagitated major depressive disorder. The presence of at least 2 manic/hypomanic symptoms in the index episode was associated with a higher rate of family history of bipolar I disorder, a higher score for suicidal thoughts during the episode, a longer duration of the episode, and a higher affective morbidity during the observation period. CONCLUSION: The diagnosis of agitated major depressive disorder is not uncommon and has significant therapeutic and prognostic implications. The subgroup of patients with at least 2 manic/hypomanic symptoms may suffer from a mixed state and/or belong to the bipolar spectrum.     

Double-blind comparison of the continued use of antipsychotic treatment versus its discontinuation in remitted manic patients

OBJECTIVE: The goal of this study was to determine the benefits of the continued use of a typical antipsychotic agent following remission from an acute manic episode. METHOD: Immediately following remission of a manic episode treated with the combination of a typical antipsychotic (perphenazine) and a mood stabilizer (lithium, carbamazepine, or valproate), 37 patients were randomly assigned to 6 months of double-blind treatment in which in addition to the mood stabilizer they received either continued perphenazine treatment or placebo. RESULTS: Patients randomly assigned to continue perphenazine treatment, relative to those who discontinued it, were more likely to have a shorter time to depressive relapse, discontinue the study, and have increased rates of dysphoria, depressive symptoms, and extrapyramidal symptoms. CONCLUSIONS: There were no short-term benefits with the continued use of a typical antipsychotic after achieving remission from an episode of acute mania. In fact, its continued use was associated with detrimental effects.     

Vulnerability to psychosis in patients attending primary and psychiatric care. Results of the RADEP study

We studied occurrence of psychotic symptoms and their associations with occurrence of depressive and manic symptoms; 563 patients attending primary care (PrC) and 163 patients attending psychiatric outpatient care (PsC) completed a questionnaire including lists of psychotic, manic and depressive symptoms, and patients with depressive symptoms were interviewed using the same questionnaire 6 months after baseline examination. Of PrC patients, 8.5% and of PsC patients, 36.2% reported at least seven lifetime psychotic symptoms. During the 6-month follow-up, the corresponding figures were 0.22% for PrC and 2.84% for PsC patients. Among PrC patients, men, young, never-married, students and unemployed reported more psychotic symptoms than others. In multivariate analyses, occurrence of psychotic symptoms was associated with young age, never being married, poor functioning and former psychiatric treatment, as well as with occurrence of manic and depressive symptoms. Psychotic symptoms are rather prevalent in primary care and very common in psychiatric care. In primary care, vulnerability to psychosis is associated with the patient's background more strongly than in psychiatric care. Concurrent occurrence of psychotic symptoms with manic and depressive symptoms is common.