PubMed Health⌕ Search

Biomedical subjects

Frederick K Goodwin

Publications and source records attributed to Frederick K Goodwin.

At least 19 recordsLinked to original sources
PubMed2006

Extrapyramidal side effects with atypical neuroleptics in bipolar disorder.

OBJECTIVE: To examine, in a real-world clinical setting, the risk of extrapyramidal symptoms (EPS) with atypical neuroleptics in bipolar patients. METHODS: The authors assessed 51 individual patient trials of atypical neuroleptic agents (17 risperidone, 13 olanzapine, 11 quetiapine, 8 ziprasidone, and 2 aripiprazole) in 37 bipolar patients (type I or type II). Risk of EPS was assessed using the Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale, and the Simpson-Angus Scale. Mean duration of treatment was 25.5 weeks (range 3-107 weeks) and 60.8% of patients were female. RESULTS: 62.7% of trials resulted in moderate to severe EPS. EPS and discontinuation frequencies were similar between specific neuroleptic agents or between high potency (risperidone/ziprasidone/aripiprazole; 52.9%, 27/51 trials) and low potency (quetiapine/olanzapine; 47.1%, 24/51 trials) agents. In a multiple regression model adjusted for confounders, akathisia was less common with low potency agents. Younger age was associated with more akathisia. 31.4% (11/35) of trials discontinued due to side effects. 7.8% (4/51) of trials led to mild de novo tardive dyskinesia. CONCLUSIONS: Over one-half of bipolar patients experienced EPS in this real world clinical setting. This rate is much higher than the 5-15% range reported in clinical trials, suggesting potential problems with clinical trial generalizability.

Adult↗
PubMed2006

ACNP Task Force report on SSRIs and suicidal behavior in youth.

This Task Force report by the American College of Neuropsychopharmacology evaluates the safety and efficacy of selective serotonin reuptake inhibitor (SSRIs) antidepressants for depressed youth under 18 years. The report was undertaken after regulatory agencies in the United States and United Kingdom raised concerns in 2003 about the possibility that treatment of depression in children and adolescents with SSRIs may increase the risk of suicidal thinking or suicide attempts.

Adolescent↗
PubMed2006

Long-term lamotrigine plus lithium for bipolar disorder: One year outcome.

OBJECTIVE: To obtain pilot data in an observational setting on the use of lamotrigine plus lithium in the long-term treatment of patients with bipolar disorder, 87% of whom had failed to respond to at least one previous mood stabilizer. METHODS: Charts of 21 patients (11 females, 10 males, mean age 43.2 years) treated with the combination of lithium and lamotrigine were reviewed retrospectively for treatment response using the Clinical Global Impression-Bipolar Disorder-Improvement scale, divided into benefit for acute depressive symptoms, acute manic symptoms, and overall illness (including prophylaxis of mood episodes). Of the 21 patients, 76% were diagnosed with bipolar I disorder, and depressive symptoms were the most common acute indication for treatment (52%). Mean doses of lithium and lamotrigine were 963 mg/day and 179 mg/day, respectively, used for a mean of 55.7 weeks. RESULTS: Acute antidepressant benefit was observed in 48% of patients, acute anti-manic benefit in 14%, and overall prophylactic benefit in 29%. Side effects were observed in 38%, with cognitive problems most common (29%). 48% discontinued combination therapy, mainly due to lack of efficacy (19%) or activation of manic-like symptoms (19%). CONCLUSIONS: Among a group of largely treatment-resistant bipolar patients, the combination of lithium and lamotrigine appeared effective for acute depressive symptoms in about half of the patients, but acute anti-manic and long-term prophylactic efficacy appeared less robust.

Adult↗
PubMed2006

Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review.

OBJECTIVES: To update and extend comparisons of rates of suicides and suicide attempts among patients with major affective disorders with versus without long-term lithium treatment. METHODS: Broad searching yielded 45 studies providing rates of suicidal acts during lithium treatment, including 34 also providing rates without lithium treatment. We scored study quality, tested between-study variance, and examined suicidal rates on versus off lithium by meta-analytic methods to determine risk ratios (RRs) and 95% confidence intervals (CI). RESULTS: In 31 studies suitable for meta-analysis, involving a total of 85,229 person-years of risk-exposure, the overall risk of suicides and attempts was five times less among lithium-treated subjects than among those not treated with lithium (RR = 4.91, 95% CI 3.82-6.31, p < 0.0001). Similar effects were found with other meta-analytic methods, as well as for completed versus attempted suicide, and for bipolar versus major mood disorder patients. Studies with higher quality ratings, including randomized, controlled trials, involved shorter exposures with somewhat lesser lithium superiority. Omitting one very large study or those involving lithium-discontinuation had little effect on the results. The incidence-ratio of attempts-to-suicides increased 2.5 times with lithium-treatment, indicating reduced lethality of suicidal acts. There was no indication of bias toward reporting positive findings, nor were outcomes significantly influenced by publication-year or study size. CONCLUSIONS: Risks of completed and attempted suicide were consistently lower, by approximately 80%, during treatment of bipolar and other major affective disorder patients with lithium for an average of 18 months. These benefits were sustained in randomized as well as open clinical trials.

Bipolar Disorder↗
PubMed2006

Substance use disorder and other predictors of antidepressant-induced mania: a retrospective chart review.

OBJECTIVE: To determine if substance use disorder (SUD) is a predictor of antidepressant-induced mania (ADM) in bipolar disorder, correcting for confounding factors in a regression model. METHOD: 335 antidepressant trials were identified in 98 patients treated in an academic bipolar specialty clinic from 2000 to 2004. Patient charts were reviewed, and histories of SUD and ADM (primary outcome; defined as a hypomanic or manic episode within 12 weeks of beginning an antidepressant trial) were identified. Mood disorder diagnoses were made using the Structured Clinical Interview for DSM-IV mood module, and SUD diagnoses were defined using DSM-IV criteria. Potential confounding variables were also examined and included in a multivariable regression model. Concomitant mood stabilizer, antimanic, and antidepressant use was adjusted for in the regression model. RESULTS: In univariate analyses, there was no evidence of an association between ADM and past SUD. However, after adjustment for confounding variables in a multivariable regression model, there was a strong relationship (OR = 5.06, 95% CI = 1.31 to 19.64, p < .05). Other statistically significant predictors of ADM in the regression model were type II subtype of bipolar illness, female gender, and tricyclic antidepressant (TCA) use (vs. bupropion). CONCLUSIONS: Along with other factors, a history of SUD was a strong predictor of ADM. Possible underestimation of ADM in randomized clinical trials may occur due to the exclusion of subjects with SUD. Type II illness, female gender, and TCA use also appeared to be predictors of ADM, while bupropion use appeared to predict lower likelihood of ADM.

Adolescent↗
PubMed2004

Bipolar spectrum disorder: a pilot study.

OBJECTIVE: To assess depressive features of a proposed definition of bipolar spectrum disorder (BSD). METHODS: Thirty-six patients with bipolar disorder type I or II were compared to 37 patients with unipolar major depressive disorder through patient interview and chart review. RESULTS: Univariate analysis suggests that 7 of 12 (recurrent major depressive episodes, brief major depressive episodes, atypical depressive symptoms, early age of onset, family history of bipolar disorder, antidepressant tolerance, and antidepressant-induced mania) features of major depressive episodes were more likely to occur in bipolar versus unipolar patients. After adjustment in a multivariable regression model, however, the five most powerful predictors of bipolar disorder were brief major depressive episodes, early age of onset, antidepressant- induced mania, postpartum depression, and atypical depressive symptoms. CONCLUSIONS: This preliminary study supports the idea that bipolar disorder is characterized by some depressive features less likely to be found in unipolar depression. Further prospective study needs to be conducted comparing BSD with unipolar depression.

Adult↗
PubMed2004

Separate and concomitant use of lamotrigine, lithium, and divalproex in bipolar disorders.

Expert consensus emphasizes the need for better recognition and accurate diagnosis of bipolar disorder. Current research on lithium, divalproex, and lamotrigine provides new insight into the effective management of this illness. Advances in identifying the mechanism of action of mood stabilization has focused on signaling pathways within the cell that are associated with neurotrophic effects. Clinical research has led to confirmatory evidence of the efficacy of lithium in all phases of bipolar disorder, with the greatest effects seen in the treatment and prevention of mania. Compared to divalproex, lithium also has been found to have greater efficacy in the prevention of suicide. Lamotrigine has emerged as a first line treatment for bipolar depression, which is an area of weakness for other mood stabilizers. Oral loading of divalproex leads to rapid stabilization of mania without imposing a greater adverse effect burden than conventional dosing. Because no agent is universally effective in all phases of the illness, combination therapy with two or more agents often is the best option.

Acute Disease↗
PubMed2004

Use of olanzapine in the treatment of bipolar I disorder.

Olanzapine (Zyprexa, Eli Lilly & Co.) is an atypical antipsychotic medication with once-daily dosing that was originally developed for the treatment of schizophrenia. It has shown broad efficacy in the treatment of bipolar mixed and manic episodes, but is less effective in the treatment of bipolar depression. Double-blind studies have demonstrated a rapid onset of action in acute bipolar mania, significantly greater rates of response compared with placebo, and a remission rate of 88.3% in a 49-week open-label study. Diverse presentations of the illness responded well to olanzapine including patients with rapid-cycling bipolar disorder, mixed episodes, as well as psychotic and nonpsychotic manias. Olanzapine monotherapy improved symptoms of depression related to its sedating and appetite-enhancing profile, but core symptoms such as depressed mood did not improve significantly. However, in combination with fluoxetine, bipolar depressed patients responded without an increased risk of mania. Weight gain and sedation are prominent adverse effects, and it has been associated with atherogenic dyslipidemia and glucose intolerance.

Antipsychotic Agents↗
PubMed2004

Effect of lamotrigine on cognitive complaints in patients with bipolar I disorder.

BACKGROUND: This analysis describes the effects of bipolar I disorder on self-reported neurocognitive measures and remediation of these deficits with lamotrigine therapy. METHOD: Data were derived from 2 clinical trials designed to assess the efficacy of lamotrigine as maintenance therapy for recently manic (N = 349) or depressed (N = 966) patients (DSM-IV criteria). During the 8- to 16-week open stabilization phase, patients received lamotrigine as monotherapy or as adjunctive therapy (target dose = 200 mg/day, minimum dose = 100 mg/day) while other psychotropic drugs were discontinued. The Medical Outcomes Study Cognitive Scale (MOS-Cog) and the AB-Neurological Assessment Scale (AB-NAS) were used to measure cognitive functioning at baseline and at the end of the open-label phase. To examine the relationship between depressive and manic symptomatology, initiation of lamotrigine, and cognitive functioning, correlational analyses and analyses of covariance were conducted. RESULTS: Bipolar patients in both trials had significant cognitive impairment; however, it was much greater in index episode depressed bipolar patients compared with index episode manic patients. In both studies, substitution of lamotrigine for other psychotropic medications significantly improved the mean scores from baseline to the end of the open-label phase on the MOS-Cog and the AB-NAS (p < .0001). Among patients who took lamotrigine as monotherapy, the mean MOS-Cog score also improved significantly versus baseline (+32.2, or 81%, for depressed patients, p < .0001; and +19.9, or 35%, for manic patients, p < .0001). Mean AB-NAS scores (-19.7, or -55%, for depressed patients, p < .0001; and -7.2, or -32%, for manic patients, p = .0062) showed similar improvement. Cognitive impairment was significantly correlated with depression symptom severity based on Hamilton Rating Scale for Depression scores (p < .0001). After controlling for change in mood, age, gender, baseline score, duration of illness, and duration of use of other psychotropics, a significant improvement in cognition was observed during the open-label phase when lamotrigine was used as monotherapy/adjunctive therapy. CONCLUSION: Treatment with lamotrigine as monotherapy and as adjunctive therapy was associated with improved cognitive functioning and reduced neurocognitive side effects, regardless of index mood polarity.

Adult↗
PubMed2003

Suicide risk in bipolar disorder during treatment with lithium and divalproex.

CONTEXT: Several studies have suggested that lithium treatment reduces risk of suicide in bipolar disorder, but no research has examined suicide risk during treatment with divalproex, the most commonly prescribed mood-stabilizing drug in the United States. OBJECTIVE: To compare risk of suicide attempt and suicide death during treatment with lithium with that during treatment with divalproex. DESIGN AND SETTING: Retrospective cohort study conducted at 2 large integrated health plans in California and Washington. PATIENTS: Population-based sample of 20 638 health plan members aged 14 years or older who had at least 1 outpatient diagnosis of bipolar disorder and at least 1 filled prescription for lithium, divalproex, or carbamazepine between January 1, 1994, and December 31, 2001. Follow-up for each individual began with first qualifying prescription and ended with death, disenrollment from the health plan, or end of the study period. MAIN OUTCOME MEASURES: Suicide attempt, recorded as a hospital discharge diagnosis or an emergency department diagnosis; suicide death, recorded on death certificate. RESULTS: In both health plans, unadjusted rates were greater during treatment with divalproex than during treatment with lithium for emergency department suicide attempt (31.3 vs 10.8 per 1000 person-years; P<.001), suicide attempt resulting in hospitalization (10.5 vs 4.2 per 1000 person-years; P<.001), and suicide death (1.7 vs 0.7 per 1000 person-years; P =.04). After adjustment for age, sex, health plan, year of diagnosis, comorbid medical and psychiatric conditions, and concomitant use of other psychotropic drugs, risk of suicide death was 2.7 times higher (95% confidence interval [CI], 1.1-6.3; P =.03) during treatment with divalproex than during treatment with lithium. Corresponding hazard ratios for nonfatal attempts were 1.7 (95% CI, 1.2-2.3; P =.002) for attempts resulting in hospitalization and 1.8 (95% CI, 1.4-2.2; P<.001) for attempts diagnosed in the emergency department. CONCLUSION: Among patients treated for bipolar disorder, risk of suicide attempt and suicide death is lower during treatment with lithium than during treatment with divalproex.

Adolescent↗
PubMed2003

Antidepressants in bipolar disorder: the case for caution.

The 2002 American Psychiatric Association (APA) guidelines for the treatment of bipolar disorder recommended more conservative use of antidepressants. This change in comparison with previous APA guidelines has been criticized, especially from some groups in Europe. The Munich group in particular has published a critique of assumptions underlying the conservative recommendations of the recent APA treatment guidelines. In this paper, we re-examine the argument put forward by the Munich group, and we demonstrate that indeed, conceptually and empirically, there is a strong rationale for a cautious approach to antidepressant use in bipolar disorder, consistent with, and perhaps even more strongly than, the APA guidelines. This rationale is based on support for the following four propositions: (i) The risk of antidepressant induced mood-cycling is high, (ii) Antidepressants have not been shown to definitively prevent completed suicides and reduce mortality, whereas lithium has, (iii) Antidepressants have not been shown to be more effective than mood stabilizers in acute bipolar depression and have been shown to be less effective than mood stabilizers in preventing depressive relapse in bipolar disorder and (iv) Mood stabilizers, especially lithium and lamotrigine, have been shown to be effective in acute and prophylactic treatment of bipolar depressive episodes. We therefore draw three conclusions from this interpretation of the evidence: (i) There are significant risks of mania and long-term worsening of bipolar illness with antidepressants, (ii) Antidepressants should generally be reserved for severe cases of acute bipolar depression and not routinely used in mild to moderate cases and (iii) Antidepressants should be discontinued after recovery from the depressive episode, and maintained only in those who repeatedly relapse after antidepressant discontinuation (a minority we judge to represent only about 15-20% of bipolar depressed patients).

Affect↗
PubMed2003

Optimizing lithium treatment in bipolar disorder: a review of the literature and clinical recommendations.

While the past decade has witnessed a major proliferation of putative treatments for bipolar disorder, one medication--lithium--has proven its effectiveness through 50 years of clinical experience and scientific scrutiny. Unfortunately, because the generic compound, lithium, lacks the financial support of its newer, patented comparators, it is often neglected by clinicians who are exposed to continuing medical education (CME) and residency training programs that are heavily weighted towards the newer treatments. This article critically examines the medical literature on lithium's efficacy, anti-suicidal properties, and adverse effects. The authors present research-based recommendations for maximizing lithium's benefits and minimizing adverse effects associated with lithium in patients with bipolar disorder.

Journal Article↗