Lithium, valproate, and carbamazepine prescribing patterns for long-term treatment of bipolar I and II disorders: A prospective study.

OBJECTIVE: This study aims to describe the prescription patterns of the mood stabilizers most commonly used for the treatment of bipolar I and II disorders (lithium, valproate, and carbamazepine) and to analyze the treatment outcomes. METHODS: Two hundred and thirty-four outpatients with bipolar disorders receiving prophylactic treatment with lithium, valproate, carbamazepine, or their combination were followed up for at least 18 months in two Italian psychiatric centers specialized in mood disorders. RESULTS: The combination of lithium and valproate or carbamazepine was the most common prophylactic treatment (54.3%), followed by valproate or carbamazepine (24%) and lithium monotherapy (22%). Polytherapy was prescribed mainly to patients with bipolar I disorder, a high number of previous episodes and lifetime psychotic symptoms, whereas valproate or carbamazepine monotherapy was prescribed to patients with anxiety comorbidity. The annual frequency of recurrences decreased significantly after entering the study in the overall sample, and the reduction was significantly higher in patients on lithium plus valproate or carbamazepine compared with the valproate or carbamazepine group, but not with the lithium monotherapy group. The number of mixed recurrences during the follow-up was significantly higher in patients on lithium plus valproate or carbamazepine. CONCLUSIONS: Our findings may help clinicians to personalize long-term treatment to prevent relapses of bipolar disorder according to clinical presentation.

[Long-term treatment of bipolar disorder: how should we use lithium salts?]. / Trattamento a lungo termine del disturbo bipolare: quale impiego dei sali di litio nella pratica clinica?

UNLABELLED: Despite the great quantity of evidence supporting the efficacy of lithium in the maintenance treatment of bipolar disorder (BD), its use has often been limited because of issues about the management of this compound. W aimed to evaluate the use of lithium in common clinical practice and to identify possible relationships between the trend over time of serum lithium levels and clinical course of the illness. METHODS: 98 patients with bipolar I and bipolar II disorder (DSM-IV-TR) on maintenance treatment with lithium salts were recruited and followed up in a naturalistic trial at the Day Hospital of Psychiatric Clinic of Pisa. Diagnosis was confirmed using a structured interview, the SCID-I. During symptom assessment, the Clinical Global Impression-Bipolar Version Scale (CGI-BP) was used. RESULTS: The sample is made up mainly of BI patients (87.8%) and lithium is used in association with anticonvulsants in 63%. Less than half of the sample (48%) presents average serum lithium levels in the therapeutic range (0.5-0.8 mEq/L); serum values of lithium within the range were seen more frequently in patients with manic/mixed episode, with manic/mixed polarity of onset, with a greater number of previous episodes, with a higher percentage of rapid cycling and in subjects treated with lithium associated with anticonvulsants. During the follow-up patients with average serum lithium levels within the therapeutic range obtained a clinical improvement in a significantly greater proportion compared to patients with average serum lithium levels lower than 0.50 mEq/L. DISCUSSION: In clinical practice, lithium is often used at doses determining serum levels at the lower limits of the therapeutic range. Preliminary data on the prospective course of the illness support the importance of maintaining serum values of lithium within the therapeutic range.

Adult separation anxiety in patients with complicated grief versus healthy control subjects: relationships with lifetime depressive and hypomanic symptoms.

BACKGROUND: Around 9% to 20% of bereaved individuals experience symptoms of complicated grief (CG) that are associated with significant distress and impairment. A major issue is whether CG represents a distinctive nosographic entity, independent from other mental disorders, particularly major depression (MD), and the role of symptoms of adult separation anxiety. The purpose of this study was to compare the clinical features of patients with CG versus a sample of healthy control subjects, with particular focus on adult separation anxiety and lifetime mood spectrum symptoms. METHODS: A total of 53 patients with CG and 50 healthy control subjects were consecutively recruited and assessed by means of the Structured Clinical Interview for DSM-IV Axis-I disorders (SCID-I/P), Inventory of Complicated Grief (ICG), Adult Separation Anxiety Questionnaire (ASA-27), Work and Social Adjustment Scale (WSAS) and Mood Spectrum-Self Report (MOODS-SR) lifetime version. RESULTS: Patients with CG reported significantly higher scores on the MOODS-SR, ASA-27, and WSAS with respect to healthy control subjects. The scores on the ASA-27 were significantly associated with the MOODS-SR depressive and manic components amongst both patients and healthy control subjects, with a stronger association in the latter. CONCLUSIONS: A major limitation of the present study is the small sample size that may reduce the generalizability of the results. Moreover, lifetime MOODS-SR does not provide information about the temporal sequence of the manic or depressive symptoms and the loss. The frequent comorbidity with MD and the association with both depressive and manic lifetime symptoms do not support the independence of CG from mood disorders. In our patients, CG is associated with high levels of separation anxiety in adulthood. However, the presence of lifetime mood instability, as measured by the frequent presence of depressive and hypomanic lifetime symptoms, suggests that cyclothymia might represent the common underlying feature characterizing the vulnerability to both adult separation anxiety and CG.

Predictors of recurrence during long-term treatment of bipolar I and II disorders. A 4 year prospective naturalistic study.

BACKGROUND: Despite the large number of treatments available for bipolar disorder (BD), more than one half of patients have a recurrence within 2 years, and over 90% experience at least one additional affective episode during their lifetime. METHODS: The aim of this study was to test the impact of a number of demographic and clinical features on the risk to recurrence in a real- word representative sample of 266 outpatients with BD-I or II treated in a naturalistic setting during a 4-years-follow-up period. RESULTS: We found that the number of episodes per year after study entry, compared to the number of episodes per year before study entry,significantly decreased and that about one third of patients had no recurrences during the observation period. The length of follow-up and the number of previous episodes, mainly depressive, predicted the risk of recurrence, while female gender, higher age at intake, and a higher frequency of past mixed episodes predicted a higher frequency of recurrences. LIMITATIONS: The study had some limitations to consider: i.e. the risk of poor reliability of information on the previous course of illness or the naturalistic treatment during the follow-up. CONCLUSIONS: Our study suggests that (a) an evidence-based long-term treatment, with regular follow-up visits could improve the course of disease and prognosis; (b) clinicians should carefully consider the presence of a high number of mixed episodes, to provide more targeted treatment strategies; (c) an appropriate use of antidepressants in selected patients did not worsen the course of illness.

Serum uric acid levels and different phases of illness in bipolar I patients treated with lithium.

Recent findings support the role of purinergic system dysfunction in the pathophysiology of bipolar disorder (BD). The present study aimed to evaluate the pattern of serum uric acid levels in a sample of 98 BD I patients followed-up prospectively in a naturalistic study and treated with lithium monotherapy or in association with other mood stabilizers (valproate or carbamazepine), in relation to different phases of illness and to pharmacological treatment. The results showed that uric acid levels were significantly higher in patients suffering from a manic/mixed episode, than in those euthymic or during a depressive phase. Further, these levels were related to the Clinical Global Impression-Bipolar Version (CGI-BP) scale score for the severity of manic symptoms. A positive correlation was found also with male sex and with serum lithium levels. These findings suggest that a dysregulation of the purinergic system may occur during manic/mixed episodes, and they support a possible role of serum uric acid levels as a state-dependent marker of BD manic phases.

Prescribing patterns of lithium or lithium+valproate in manic or mixed episodes: a naturalistic study.

The present study aimed to identify the prescribing patterns of lithium or of lithium+valproate in 75 bipolar I outpatients in a manic or a mixed phase within a naturalistic setting. The differences between the two treatments and the correlation between serum lithium levels and response were also examined. The results showed that patients with lithium levels of 0.60 mEq/l or more had higher remission rates and greater symptom reduction than the other patients. Patients on lithium and valproate showed greater improvement in mixed, anxiety, and psychotic symptoms than those on lithium only, as assessed by the Clinical Global Impression-Bipolar version scale scores. Finally, our findings suggest that a range of lithium levels between 0.40 and 0.60 mEq/l, albeit below the therapeutic range, seems sufficient to maintain a good effect when lithium is coadministered with valproate.