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Biomedical subjects

L Tondo

Publications and source records attributed to L Tondo.

At least 19 recordsLinked to original sources
PubMed2006

Comorbid substance-use in schizophrenia: relation to positive and negative symptoms.

As substance use disorders (SUD) are common in schizophrenia patients, we tested the hypothesis that comorbid patients (SUD[+]) have more positive vs. negative symptoms than non-comorbid (SUD[-]) patients. From reports identified by literature-searching we compared Positive and Negative Syndrome Scale (PANSS) ratings in schizophrenia patients with and without SUD using meta-analytic methods. Among 9 comparisons (N=725 subjects), SUD[+] patients were more often men, and abused alcohol>cannabis>cocaine. SUD[+] patients had very significantly higher PANSS-positive, and lower PANSS-negative scores. Comorbid SUD in schizophrenia patients was associated with male sex and higher PANSS positive to lower negative scores. Cause-effect relationships remain to be clarified.

Adult↗
PubMed2003

Rapid-cycling bipolar disorder: effects of long-term treatments.

OBJECTIVE: To compare responses to long-term treatment of rapid-cycling (RC) vs. non-RC bipolar disorder patients and assess relative effectiveness of specific agents in RC patients. METHOD: Studies identified by literature searching were analyzed for effects of RC status and treatment-type on clinical outcome (recurrence or non-improvement per exposure-time), using random-effects methods to estimate pooled rates and their 95% CI for quantitative meta-analytic modeling. RESULTS: Data were obtained from 16 reports with 25 trial-arms involving 1856 (905 RC and 951 non-RC) patients treated with carbamazepine, lamotrigine, lithium, topiramate, or valproate, alone or with other agents over an average of 47.5 months (7347 total patient-years). Estimated RC prevalence was 15.4%. Crude rates (%/month) of recurrence (2.31/1.20) and clinical non-improvement (1.93/0.49) averaged 2.9-fold greater in RC vs. non-RC subjects. The pooled RC/non-RC risk ratio (RR) for inferior treatment-response (in 13 direct comparisons) was 1.40 (CI 1.26-1.56; P < 0.0001). Pooled crude recurrence and non-improvement rates suggested no clear advantage for any treatment, nor superiority for anticonvulsants over lithium. However, only lithium vs. carbamazepine could be directly compared (in four treatment-arms) meta-analytically in RC patients (RR = 0.93, CI 0.74-1.18, indicating no difference in effectiveness). CONCLUSION: As expected, RC was associated with lower effectiveness of all treatments evaluated. Direct comparisons of specific treatment alternatives for RC patients were rare, and provided no secure evidence of superiority of any treatment. Additional long-term studies comparing RC/non-RC patients randomized to specific treatments are required.

Bipolar Disorder↗
PubMed2001

Response to lithium maintenance treatment in bipolar disorders: comparison of women and men.

OBJECTIVES: Possible sex differences in responses to mood-stabilizing treatment remain poorly defined. Since women with bipolar disorder reportedly have more features that may predict a poor prognosis (depression and rapid cycling), we tested the hypothesis that women respond less well to lithium maintenance treatment. METHODS: Clinical characteristics of 360 women and men with DSM-IV bipolar I or II disorder were compared before and during clinical lithium maintenance monotherapy in a mood disorders clinic by preliminary bivariate comparisons, multivariate analysis, and survival analysis of time stable during treatment. RESULTS: Women (n = 229) versus men (n = 131) were: more likely to have type II disorder (1.6 times), 3.2 years older at illness onset, more often depressed-before-manic (1.4 times), considered unipolar depressive 1.9 years longer and started maintenance treatment 5.5 years later. However, women differed little from men before treatment in overall morbidity, average episode frequency and risk of suicide attempts. Contrary to prediction, women showed non-significantly superior responses to lithium treatment, and a significant 60% longer median time before a first recurrence during treatment, despite 7% lower average serum lithium concentrations. CONCLUSIONS: Women were diagnosed as bipolar later than men with corresponding delay of lithium maintenance treatment that proved to be at least as effective as in men.

Adolescent↗
PubMed2001

Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis.

OBJECTIVE: To compare suicide rates with vs. without long-term lithium treatment in major affective disorders. METHOD: Broad searching yielded 22 studies providing suicide rates during lithium maintenance; 13 also provide rates without such treatment. Study quality was scored, between-study variance tested, and suicide rates on vs. off lithium examined by meta-analyses using random-effects regression methods to model risk ratios. RESULTS: Among 5647 patients (33 473 patient-years of risk) in 22 studies, suicide was 82% less frequent during lithium-treatment (0.159 vs. 0.875 deaths/100 patient-years). The computed risk-ratio in studies with rates on/off lithium was 8.85 (95% CI, 4.12-19.1; P<0.0001). Higher rates off-lithium were not accounted for by treatment-discontinuation. CONCLUSION: Suicide risk was consistently lower during long-term treatment of major affective illnesses with lithium in all studies in the meta-analysis, including the few involving treatment-randomization.

Adult↗
PubMed2001

Treating the suicidal patient with bipolar disorder. Reducing suicide risk with lithium.

Bipolar disorder is associated with increased mortality because of complications of commonly comorbid substance use and stress-sensitive medical disorders as well as accidents and very high rates of suicide. Long-term lithium treatment may be associated with reduced suicidal risk. We review and summarize findings that help to quantify relationships between the presence versus the absence of lithium maintenance and suicides or attempts in patients with bipolar or other major affective disorders. Results from 33 studies (1970-2000) yielded 13-fold lower rates of suicide and reported attempts during long-term lithium treatment than without it or after it was discontinued. Although greatly reduced, these rates remain above those estimated for the general population. Evidence for substantial, if incomplete, protection against suicide with lithium is supported by more compelling evidence than that for any other treatment provided for patients with mood disorders. Studies of commonly used, but incompletely evaluated, alternative treatments are required, and further protection against premature mortality can be anticipated with better protection against bipolar depression.

Antimanic Agents↗
PubMed2001

Long-term clinical effectiveness of lithium maintenance treatment in types I and II bipolar disorders.

Background The effectiveness of lithium is being questioned increasingly and requires clarification. Aims To assess the effectiveness of lithium treatment in depression and mania, syndromal types I and II, with predominantly mixed or psychotic episodes or rapid cycling, during treatment resumed following discontinuation, and across three decades. Method The longitudinal course of 360 patients with bipolar disorder compliant with lithium treatment for at least I year and without comorbidity for substance use disorder was reviewed. Results Risk of single-episode recurrences, a common index of treatment failure, was similar to that in other reports. Both episode frequency and 'time ill' improved more in type II than type I cases. Reduced morbidity during treatment was similar in patients with mixed or psychotic episodes, or rapid cycling, and in less complex cases. Retreatment yielded minor decrements in response, and there was no tendency for lesser responses in more recent years. Conclusions Based on overall affective morbidity, long-term lithium treatment in compliant patients without comorbid substance use disorder, though imperfect, remains effective, even in subgroups of supposedly poor prognosis.

Journal Article↗
PubMed2001

Long-term clinical effectiveness of lithium maintenance treatment in types I and II bipolar disorders.

BACKGROUND: The effectiveness of lithium is being questioned increasingly and requires clarification. AIMS: To assess the effectiveness of lithium treatment in depression and mania, syndromal types I and II, with predominantly mixed or psychotic episodes or rapid cycling, during treatment resumed following discontinuation, and across three decades. METHOD: The longitudinal course of 360 patients with bipolar disorder compliant with lithium treatment for at least 1 year and without comorbidity for substance use disorder was reviewed. RESULTS: Risk of single-episode recurrences, a common index of treatment failure, was similar to that in other reports. Both episode frequency and 'time ill' improved more in type II than type I cases. Reduced morbidity during treatment was similar in patients with mixed or psychotic episodes, or rapid cycling, and in less complex cases. Retreatment yielded minor decrements in response, and there was no tendency for lesser responses in more recent years. CONCLUSIONS: Based on overall affective morbidity, long-term lithium treatment in compliant patients without comorbid substance use disorder, though imperfect, remains effective, even in subgroups of supposedly poor prognosis.

Adult↗
PubMed2001

Pharmacologic interventions in suicide prevention.

Suicide rates vary by country and by mental disorder. What does not vary, though, is that the number of suicides per year is not declining and that a person with a mental disorder is more likely to commit suicide than one without such an illness. Although many pharmacologic interventions have been reported to reduce the risk of suicide among mentally ill patients, especially those with bipolar disorder, the effects of such interventions are inconsistent at best. Lithium is the only medication for which the evidence consistently shows an antisuicidal effect.

Antidepressive Agents↗
PubMed2000

Does lithium treatment still work? Evidence of stable responses over three decades.

To evaluate whether lithium treatment has been overvalued and may be no longer as effective as formerly, we reviewed published reports on long-term lithium treatment (1970-1996) as well as analyzing its clinical effects on 360 patients with DSM-IV bipolar disorder who entered into lithium maintenance monotherapy after 1970. Neither reported recurrence rates nor average proportions of time ill nor patient improvement of 50% or more during lithium maintenance therapy in a stable clinic setting has changed significantly since the 1970s. Unfavorable results in some settings may reflect accumulation over time of patients with complex, less treatment-responsive illnesses. Lithium is unmatched in research support for long-term clinical effectiveness against morbidity and mortality associated with depression or mania in bipolar I and II disorders. Data evaluated herein did not support suggestions that benefits of lithium have been exaggerated in the past or have been lost recently.

Adult↗
PubMed2000

Effects of rapid cycling on response to lithium maintenance treatment in 360 bipolar I and II disorder patients.

INTRODUCTION: Rapid cycling (RC) in bipolar disorders is widely believed to predict future morbidity and poor treatment response, although empirical testing of its predictive utility remains limited. METHODS: In 360 DSM-IV bipolar I (N=218) and II (N=142) disorder subjects (64% women) followed over an average of 13.3 years, we evaluated factors associated with RC status with bivariate and multivariate techniques, and response to lithium maintenance treatment (recurrence rates, time ill, survival analysis of time to recurrence on lithium). RESULTS: RC risk (15.6% of cases) was 5. 1-times greater in bipolar II vs. I subjects (30.3%/6.0%), in minor excess in women vs. men (17.9%/11.5%), and associated with premorbid cyclothymia, depressive first episodes, older onset age, and being employed or married. Before lithium, RC vs. non-RC cases had more mean total (3.9/1.2), manic, and depressive episodes/year, and greater percent time ill (60%/38%). During treatment, prior RC status was unrelated to time to first recurrence and other measures of morbidity and improvement including percent time ill, although depressive episodes were 2.7-times more frequent, and there was 13.7% less chance of full protection from all recurrences in RC cases. LIMITATIONS: The study is naturalistic, without random assignment or blind assessment. CONCLUSIONS: The RC bipolar subtype was strongly associated with type II diagnosis, higher average prelithium episode frequency and percent time ill, and weakly with female sex, but not with greater overall morbidity during treatment.

Antimanic Agents↗
PubMed2000

Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance.

OBJECTIVE: Pregnancy poses major challenges for the treatment of bipolar disorder, and information to guide clinical care remains very sparse. The authors sought to determine the illness recurrence risk for women with bipolar disorder who discontinue lithium maintenance during pregnancy. METHOD: The authors retrospectively compared recurrence rates and survival functions for 101 women with DSM-IV bipolar disorder (68 type I, 33 type II) during pregnancy and postpartum (N=42) or during equivalent periods (weeks 1-40 and 41-64) for age-matched nonpregnant subjects (N=59) after either rapid (1-14 days) or gradual (15-30 days) discontinuation of lithium. Recurrence rates also were obtained for the year before discontinuing lithium. RESULTS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant (52%) and nonpregnant women (58%) but had been much lower for both in the year before treatment was discontinued (21%). Among subjects who remained stable over the first 40 weeks after lithium discontinuation, postpartum recurrences were 2.9 times more frequent than recurrences in nonpregnant women during weeks 41-64 (70% versus 24%). Depressive or dysphoric-mixed episodes were more prevalent in pregnant than nonpregnant women (63% versus 38% of recurrences). Recurrence risk was greater after rapid than after gradual discontinuation, and for patients with more prior affective episodes, but was similar for diagnostic types I and II. CONCLUSIONS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant and nonpregnant women but then sharply increased postpartum. Risk was much lower during preceding treatment and less with gradual discontinuation. Treatment planning for potentially pregnant women with bipolar disorder should consider the relative risks of fetal exposure to mood stabilizers versus the high recurrence risks after discontinuing lithium.

Age of Onset↗
PubMed2000

Sex differences in response to lithium treatment.

OBJECTIVE: Although sex differences occur with some psychotropic drug treatments, they are not well defined for mood-stabilizing agents, including lithium. The authors' goal was to investigate whether there are differences between the sexes in response to lithium. METHOD: Studies identified in a literature search were analyzed for reports of sex differences in clinical response to lithium in major affective syndromes. RESULTS: Data from 17 studies published in 1967-1998, involving 1,548 adults treated with lithium for a mean of 38.6 months (SD=30.5), yielded similar weighted response rates to lithium in 1,043 women (65.6% [N=684]) and 505 men (61.0% [N=308]). CONCLUSIONS: The results indicate little difference between the sexes in clinical response to lithium treatment of bipolar and related affective disorders.

Adult↗
PubMed2000

Reduced suicide risk during lithium maintenance treatment.

BACKGROUND: About 20% of deaths of bipolar disorder patients are suicides associated with depressive or mixed episodes. Long-term lithium treatment may be associated with reduction of suicidal risk. METHOD: We reviewed studies and our previously reported data to quantify relationships of presence versus absence of lithium maintenance and suicides or suicide attempts in bipolar disorder patients. RESULTS: Results from 22 studies (1974-1998) yielded 7-fold lower suicidal rates for patients during long-term lithium treatment than for these patients when they were not receiving such treatment, patients lacking such treatment, or for patients after lithium discontinuation. CONCLUSIONS: Protection against suicide with lithium is incomplete, but rates of suicides plus attempts during lithium treatment may approach general population base rates. Better protection against bipolar depression is essential for limiting suicidal risk: alternatives to lithium require further study for effects on suicidal behavior.

Adolescent↗
PubMed1999

Latency and episodes before treatment: response to lithium maintenance in bipolar I and II disorders.

OBJECTIVES: To test whether longer treatment-delays or more pretreatment illness episodes are followed by diminished response to lithium maintenance. METHODS: In 360 DSM-IV bipolar I (n = 220) or II (n = 140) patients, effects of latency from illness onset to starting lithium and number of pretreatment episodes were evaluated by survival analysis based on the number of months stable before a first recurrence on lithium. Factors associated with treatment latency were identified by regression modeling. Relationships of time, episode number, and morbidity before treatment to the overall proportion of time ill on lithium were also tested by nonparametric correlation. RESULTS: Latency to first lifetime lithium maintenance averaged 8.3 years, with 9.3 episodes/subject. Time stable before a first recurrence on lithium averaged 29.6 months and was unrelated to treatment latency (in terciles) or to a high (> or = ten), intermediate (four-nine), or low (< four) number of prior episodes. Overall morbidity during 4.6 years of lithium maintenance was also unrelated to these pretreatment factors. More episodes/year and percentage of time ill before treatment anticipated shorter treatment latency, with greater relative improvement, but were unrelated to morbidity during treatment. CONCLUSIONS: Treatment latency and prelithium episode number were unrelated to morbidity during treatment. Although multiple untreated episodes can lead to severe disability, lithium evidently can greatly limit morbidity, even after years of delay and multiple episodes of bipolar illness.

Adult↗
PubMed1999

Discontinuing lithium maintenance treatment in bipolar disorders: risks and implications.

OBJECTIVE: To review research findings on clinical effects of discontinuing lithium maintenance treatment. METHODS: Data from studies reported since 1970 plus our recent findings were updated. RESULTS: Discontinuing lithium maintenance treatment led to marked increases of early affective morbidity and suicidal risk. Gradual discontinuation markedly reduced early recurrences of mania or depression, did so more in bipolar II than I disorder patients, and also tended to reduce suicidal risk. Similar effects were found in pregnant and nonpregnant women after lithium discontinuation. Long-term retreatment with lithium following discontinuation was only slightly less effective than in initial trials. CONCLUSIONS: Recurrences increased sharply soon after discontinuing lithium, but were markedly limited and not merely delayed, by slow discontinuation. Similar reactions may follow discontinuation of other drugs, evidently as responses to long-term pharmacodynamic adaptations. Discontinuing treatment is not equivalent to not-treating. Post-discontinuation relapse risk has implications for the design, management, and interpretation of protocols involving discontinuation of long-term treatments that should be considered in both clinical management and research.

Antimanic Agents↗