An open trial of pregabalin as an acute and maintenance adjunctive treatment for outpatients with treatment resistant bipolar disorder.

BACKGROUND: Pregabalin is a structural analog of GABA, similar to gabapentin. It does not have a FDA indication for any psychiatric disorder in the USA. There has been one case report of the successful use of pregabalin as an augmenting agent in a patient with Bipolar Disorder (BD). In the present open label study, not subsidized by the manufacturer, the investigators prospectively evaluated the acute and maintenance efficacy of pregabalin as an adjunctive medication for a group of treatment refractory outpatients with BD. METHODS: Older adolescent and adult outpatients with any type of DSM-IV diagnosed BD, who were considered treatment nonresponders to multiple standard medications for BD, were treated with adjunctive pregabalin. The baseline mood state before initiation of pregabalin was compared to the mood state after an acute trial of pregabalin using the Clinical Global Impression-Bipolar Version Scale (CGI-BP). All acute responders were treated for a minimum of two months. Follow-up maintenance treatment data was obtained for the acute pregabalin responders for three years after the 18 month acute phase of the study. RESULTS: Fifty-eight total patients were treated adjunctively with pregabalin. Twenty-four (41%) were rated as acute responders. For the acute responders, pregabalin produced either a mood stabilizing effect, antidepressant effect or antimanic effect. Intolerable side-effects were the most common reason (79%) for a failed acute trial of pregabalin. None of the side effects resulted in serious medical complications. No patient abused pregabalin, and there were no adverse drug-drug interactions despite an average of 3.3 concurrent other psychiatric medications. The maintenance data revealed that 10 (42%) of the original 24 acute pregabalin responders were still taking pregabalin as an add-on medicine for an average of 45.2 months (range 42-48, SD: 2.35). LIMITATIONS: This study has an open label observation design. CONCLUSIONS: The results of this preliminary open study suggest that pregabalin is a safe and effective acute and maintenance adjunctive treatment for a significant number of treatment-resistant outpatients with any type of BPD. It appears to have mood stabilizing and antidepressant properties in addition to antimanic effects. Similar studies using a double-blind, randomly controlled design would be useful to confirm the reliability and validity of the results of this study.

Efficacy and safety of nonbenzodiazepine hypnotics for chronic insomnia in patients with bipolar disorder.

BACKGROUND: Insomnia in patients with bipolar disorder (BD) can cause distress, daytime dysfunction, cognitive impairment, worsening of hypomanic/manic symptoms and increased suicide risk. Physicians often prescribe hypnotics for BD patients with insomnia although no hypnotic has a specific FDA indication for this use. In this study, the patterns of use, efficacy and safety of five nonbenzodiazepine hypnotics (NBZHs) were assessed in a large group of outpatients with BD. METHOD: A chart review was performed for all older adolescents and adult BD outpatients in a private outpatient clinic. Clinical data was collected for any patient who had ever been prescribed a NBZH for insomnia and included successful current use, past unsuccessful treatments, side effects, duration of use, concurrent psychiatric medications, and absence or presence of untoward events often associated with chronic use of hypnotics. RESULTS: A significant number of BD patients take NBZHs as needed or on a daily basis. Four NBZHs had adequate success rates; ramelteon was limited in efficacy. Some patients experienced satisfactory results from a NBZH after unsuccessful trials with one or more other NBZHs. About half of the current NBZH users are taking them on a daily long-term basis, and none of these patients have experienced unacceptable untoward events. About three quarters of the chronic NBZH users are taking antimanic medications concurrently, and less than half of the chronic users are taking antidepressants. LIMITATIONS: The results may not be generalizable to other BD populations. A control group was not included in the design. Chronic users of NBZHs were not asked to discontinue their NBZH in order to confirm indication for long-term use. CONCLUSIONS: Most NBZHs can be effective and safe agents for selected BD outpatients with episodic or chronic insomnia. Failure to respond to one or more NBZH does not preclude a satisfactory response to a different NBZH. Some BD patients who take maintenance antimanic agents also require NBZH treatment. Overactivation from antidepressant treatment does not contribute to chronic NBZH use in most BD patients.

Psychiatric reactions to isotretinoin in patients with bipolar disorder.

BACKGROUND: Isotretinoin (Accutane(R)) has been available for the treatment of severe cystic acne for about twenty-five years. There have been several reports of adverse psychiatric reactions to isotretinoin, including depressive symptoms and suicide. However, there have been only three case reports of patients with bipolar disorder (BD) who experienced an untoward psychiatric side effect while receiving isotretinoin treatment. In this study, the psychiatric side effects from isotretinoin were assessed in a larger group of BD patients than has previously been reported. METHODS: A retrospective chart review of 300 BD outpatients identified ten patients treated with isotretinoin. RESULTS: Nine of these ten patients experienced a significant worsening of mood symptoms, and three developed suicidal ideation. Eight experienced a reversal of the relapsed mood symptoms when the isotretinoin was discontinued, whether prematurely or after a full course. LIMITATIONS: The limitations of this study include small sample size, retrospective data collection, absence of double-blind controlled design, and inability to control for spontaneous mood episodes in patients with BD. CONCLUSIONS: These results indicate that BD patients treated with isotretinoin for acne are at risk for clinically significant exacerbation of mood symptoms, including suicidal ideation, even with concurrent use of psychiatric medicines for BD. The clinical implications of this study are especially relevant to the treatment of patients with BD because acne usually occurs during adolescence, which is often the age of onset of BD and because a common side effect of lithium (a standard treatment for BD) is acne.

Mood-elevating effects of opioid analgesics in patients with bipolar disorder.

Opioids can have mood-elevating effects in healthy subjects and have been used successfully to treat refractory depressed patients. A few case reports indicate that opioid analgesics can induce mania. The authors investigated the mood reaction of opioid analgesics in patients with bipolar disorder. Nine (27%) of 33 patients who took opioid analgesics for medical reasons experienced a significant hypomanic/manic reaction, and two other patients reported an antidepressant effect. None of the comparison subjects reported a significant mood reaction from opioid analgesics. These results indicate that opioid analgesics can have an important mood-altering effect on patients with known bipolar disorder.

An open case series on the utility of tiagabine as an augmentation in refractory bipolar outpatients.

BACKGROUND: Tiagabine (Gabitril) is a GABA uptake inhibitor recently introduced in the United States as an adjunctive treatment for partial complex seizures. Three published studies have addressed the use of tiagabine for bipolar disorder (BPD); two described positive results and one negative results. We assessed the efficacy of add-on tiagabine in a larger sample of adult BPD outpatients. METHODS: Twenty-two adult outpatients with DSM-IV diagnosed BPD of some type who were considered unsatisfactory responders to standard medications for BPD were treated in an open fashion with adjunctive tiagabine in a low-dose range. After baseline demographic data and mood state at the time of entry were documented, each patient was monitored clinically for at least 6 months while the dose of tiagabine was adjusted according to the patient's clinical status. The subjects were rated using the clinical global impression-bipolar version scale (CGI-BP). RESULTS: After 6 months, eight (36%) of the patients were responders to tiagabine by CGI-BP rating. The dose range of tiagabine for responders was 1-8 mg per day. All 14 nonresponders had to discontinue tiagabine because of unacceptable but reversible side effects; one nonresponder experienced breakthrough absence seizures. LIMITATIONS: This study was performed in a nonrandom, open naturalistic clinical setting. The sample size was small. CONCLUSIONS: Low-dose tiagabine appears to have mood-stabilizing and antimanic properties as an add-on medication for some adult outpatients who have BPD refractory to standard medications. Tiagabine appears to be safe for most adult BPD outpatients. The results of this preliminary open study await confirmation by double-blind controlled studies.