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Biomedical subjects

L Tondo

Publications and source records attributed to L Tondo.

At least 37 records · Page 2Linked to original sources
PubMed1999

Suicide attempts in major affective disorder patients with comorbid substance use disorders.

BACKGROUND: The widely accepted impression that substance abuse and dependence are associated with increased suicidal risk was evaluated by literature review and with new data. METHOD: Previous research on this association was reviewed, and clinical data on suicide attempts and substance use in 504 mood disorder patients hospitalized in 4 psychiatric units in Sardinia affiliated with the Italian mental health system were analyzed. RESULTS: The literature supports associations of alcohol and drug use comorbidity with major affective disorders, and of some substances (polyabuse, alcohol, heroin, cocaine, and even tobacco, but perhaps not marijuana or hallucinogens) with suicidal behavior. Our new findings generally supported these 2-way associations. Suicidal risks were similar in hospitalized men and women but were associated with bipolar II, bipolar I (mainly mixed), and unipolar depressive disorders as well as substance abuse, with little effect of type of agent. Substance abuse was more common in nonmixed bipolar disorders, men, and age below 30. CONCLUSION: The tendency for bipolar I, mainly nonmixed patients, to have a relatively high risk of substance abuse and low risk of suicide attempts indicates that mainly depressive or dysphoric (bipolar II, nonbipolar, and bipolar I, mainly mixed) mood disorders may be especially lethal. Differences in risks of substance abuse and suicidal behavior in men and in bipolar I patients further suggest that substance abuse and mood disorders may contribute to suicidal risk with at least partial independence or additivity.

Adult↗
PubMed1999

Effects of lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders.

BACKGROUND: Whether mood-altering treatments reduce risk of suicidal behavior remains largely unproved. METHOD: We compared suicidal rates in published studies of patients treated with lithium with those who were not, and in a mood disorders clinic before, during, and after discontinuing lithium. RESULTS: Published reports indicate a 7.0-fold lower rate of suicidal acts with lithium treatment of manic-depressive patients. In new findings in over 300 bipolar patients, latency from illness onset to lithium maintenance averaged 8.3 years (from 11.0 years in women with bipolar II disorder to 6.9 years in men with bipolar I disorder), but half of all suicidal acts occurred in the first 7.5 of 18.3 years at risk. Most acts (89%) occurred during depressive (73%) or dysphoric-mixed (16%) mood states and were associated with previous severe depression, prior attempts, and lower age at onset. Morbidity was reduced 2.7-fold and suicidal acts per year 6.5-fold during lithium treatment, with 8.3-fold cumulative sparing of risk by 15 years on lithium. In the first year off lithium, affective illness recurred in 67% of patients, and suicidal rates rose 20-fold but were much lower thereafter; fatalities were 14 times more frequent after discontinuation of lithium. Early morbidity was 2.5-fold lower, and suicidal risk was 2.0-fold lower after slow versus rapid discontinuation. CONCLUSION: Lithium maintenance is associated with sustained reduction of suicidal acts in manic-depressive disorders. Treatment discontinuation, particularly abruptly, led to early affective morbidity and suicidal behavior. Improved diagnosis and treatment as well as earlier intervention for potentially lethal bipolar depression are urgently needed, as are studies of all mood-altering agents for effects on suicidal behavior.

Bipolar Disorder↗
PubMed1998

Rapid cycling in women and men with bipolar manic-depressive disorders.

OBJECTIVE: This study investigated risks for rapid cycling, as defined by DSM-IV, in women and men with bipolar disorders. METHOD: The results of 10 studies with a total of 2,057 bipolar patients were meta-analyzed by pooled contingency methods. RESULTS: The proportions of women and men among rapid-cycling cases averaged 72% and 28%, respectively, but the risk of rapid cycling was inconsistently more frequent among women (29.6%) than among men (16.5%). The mean number of episodes per year was much higher in rapid-cycling patients before and during lithium treatment but was similar in rapid-cycling men and women. CONCLUSIONS: Rapid cycling was only moderately, and inconsistently, more common in bipolar women than men.

Bipolar Disorder↗
PubMed1998

Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders.

OBJECTIVE: Effects of long-term lithium treatment for depressive and manic phases of type I and type II bipolar disorders were compared. METHOD: Clinical research records of 317 patients with DSM-IV-defined bipolar disorder (188 with type I and 129 with type II) were analyzed for frequency and duration of affective episodes and hospitalizations before (mean = 8.38 years) versus during (mean = 6.35 years) lithium maintenance treatment. Treatment effects were also assessed by survival analysis of interepisode intervals and by multivariate regression testing for factors associated with response to treatment. RESULTS: Bipolar I and bipolar II patients were ill before treatment a similar percentage of time, but the subtype distinction was supported descriptively. Lithium had superior benefits in type II patients, with significantly greater reduction of episodes per year and of the percentage of time ill. Reduction of depressive morbidity was similarly strong in both diagnostic types. During treatment, bipolar II patients had 5.9-fold longer interepisode intervals and were twice as likely as type I patients to have no new episodes. Starting lithium maintenance earlier predicted greater improvement. CONCLUSIONS: Lithium maintenance yielded striking long-term reductions of depressive as well as manic morbidity in both bipolar disorder subtypes, with greater overall benefits in type II patients and with earlier treatment.

Adult↗
PubMed1998

Lithium treatment and risk of suicidal behavior in bipolar disorder patients.

BACKGROUND: Lithium may exert an antisuicidal effect in bipolar disorder patients, but this hypothesis requires further testing by direct comparison of patients with and without lithium treatment. METHOD: Risk of life-threatening suicidal acts over time and associated factors were analyzed in 310 patients with DSM-IV bipolar I (N = 186) or II (N = 124) disorder evaluated for a mean of 8.3 years before, and prospectively during, a mean of 6.4 years of lithium maintenance in a mood disorder clinic; 185 were also followed for a mean of 3.7 years after clinically discontinuing lithium. RESULTS: In 5233 patient-years of observation, 58 patients made 90 suicide attempts (8 were fatal). Survival analyses with Weibull modeling with adjustments for covariates indicated a highly significant 6.4-fold adjusted hazard ratio during versus before and 7.5-fold ratio after versus during lithium maintenance. Suicidal acts were more common early in the course of illness before lithium and were associated with prior suicide attempts, greater proportion of time depressed, and younger age. After the discontinuation of lithium, suicidal acts were more frequent in the first year than at later times or before start of lithium treatment. Fatalities were 9 times more frequent after versus during treatment. CONCLUSION: Lithium maintenance was associated with marked reduction of life-threatening suicidal acts, the number of which sharply increased after discontinuing lithium. Suicidal behavior was strongly associated with prior suicide attempts, more time depressed, and younger age or recent onset. Greater attention to suicidal risk in patients with bipolar depression and assessment of all proposed mood-stabilizing agents for antisuicidal effects are strongly encouraged.

Adolescent↗
PubMed1997

Effect of lithium maintenance on suicidal behavior in major mood disorders.

We reviewed evidence of a possible antisuicide action of lithium maintenance treatment in mood disorders. Of 28 published studies involving over 17,000 patients with major affective illnesses, most yielded supportive evidence: risk of suicides and attempts averaged 3.2 versus 0.37 per 100 patient-years without versus with lithium (8.6-fold difference). In a new study of 284 bipolar I- and II-disordered patients, corresponding rates (2.2 vs. 0.39/100 patient-years) differed by 5.6-fold (p < 0.001); moreover, after discontinuing lithium, rates of suicidal acts rose by 7-fold (16-fold within the first year), and fatalities increased by nearly 9-fold. Lithium maintenance treatment in recurring major mood disorders has strong evidence of antisuicide effects not demonstrated with any other mood stabilizer. Close association of suicide and depression in bipolar disorder emphasizes the need for improved identification and treatment of bipolar depression.

Bipolar Disorder↗
PubMed1997

Differential response of rapid eye movement sleep to cholinergic blockade by scopolamine in currently depressed, remitted, and normal control subjects.

The degree of cholinergic dysregulation of sleep in adult depression was evaluated using scopolamine. On separate sessions, placebo and scopolamine (4.5 micrograms/kg, IM) were administered to 14 patients with unipolar major depression, 16 recovered/remitted patients, and 18 normal controls. Scopolamine increased rapid eye movement (REM) latency (RL), reduced REM activity (RA), REM density (RD), and REM duration, and increased the percentage of stage 4 sleep in all groups. There was a differential effect of scopolamine on RL, RA, and REM duration for the first REM period, and on percentage of stage 4 sleep. Whereas a primary cholinergic hyperactivity could account for the RA and RD responses, the response profile for RL was more compatible with reduced aminergic tone as the proximal cause of the cholinergic hyperactivity. Whether the sleep abnormalities observed in remitted patients reflect an underlying vulnerability for development or recurrence of depression, and/or a scar, remains to be determined.

Adult↗
PubMed1997

Effectiveness of restarting lithium treatment after its discontinuation in bipolar I and bipolar II disorders.

OBJECTIVE: This study tested the hypothesis that resumption of lithium treatment of bipolar disorders may be less effective after maintenance treatment has been discontinued. METHOD: Eighty-six patients with type I or II bipolar disorder, not selected according to response to treatment, were followed prospectively during two periods of lithium maintenance treatment averaging 4.6 and 4.4 years. Morbidity (illness episodes per year, hospitalizations per year, percentage of time ill) was assessed, and use of adjunctive medication was rated. RESULTS: Morbidity was similar in the first and second treatment periods (mean number of episodes = 0.83 and 0.94 per year, respectively; mean percentage of time ill = 18.0% and 24.2%), with no differences in numbers of manic and depressive episodes or differences by gender, diagnostic type, length of first treatment, interval between treatments, or discontinuation rate. There was 12.8% more use of adjunctive medication in the second period. CONCLUSIONS: The efficacy of lithium did not differ significantly between the first and second treatment periods.

Adult↗
PubMed1997

Reduced morbidity after gradual discontinuation of lithium treatment for bipolar I and II disorders: a replication study.

OBJECTIVE: The aim of this study was to verify reduction of early affective morbidity by gradual, rather than rapid, discontinuation of lithium treatment. METHOD: For 78 patients with bipolar disorders, lithium treatment was discontinued either rapidly (over 1-14 days) or gradually (over 15-30 days). The effects of the two schedules were compared by survival analysis of time to first recurrence. RESULTS: Median time to recurrence was 5.6 times as long for gradual discontinuation (14.0 months) as for rapid discontinuation (2.5 months). The ratios of the median survival times for gradual and rapid discontinuation were similar in I and II subtypes and in depression and mania (4-6:1). The polarities of the episodes at onset and at first recurrence after lithium discontinuation were 83.6% concordant. CONCLUSIONS: These results independently confirm a reduction in morbid risk from slow discontinuation of lithium treatment for bipolar disorders.

Adult↗
PubMed1996

Effects of the rate of discontinuing lithium maintenance treatment in bipolar disorders.

BACKGROUND: Gradual discontinuation of lithium may reduce high risk of early morbidity in bipolar disorder patients discontinuing successful long-term maintenance on lithium, but previous small samples have limited analyses of subgroups. METHOD: DSM-IV bipolar disorder patients (N = 161) were pooled from similar samples maintained on lithium for 4.2 +/- 3.1 years. Effects of discontinuing treatment abruptly (1-14 days) or gradually (15-30 days) were compared by survival analysis in clinically closely similar groups. RESULTS: After gradual versus rapid discontinuation, the overall median time to recurrence +/- SE differed by 5.0-fold (20.0 +/- 5.8 vs. 4.0 +/- 0.7 months; p < .0001). After rapid discontinuation, the median time in remission was 2.3 times shorter than the mean cycling interval before lithium (6.3 vs. 14.6 months; p < .0001). The proportion of subjects falling ill/month (recurrence rate) was much higher in the first year after rapid discontinuation (6.5% vs. 2.3%), but similar thereafter (0.4% vs. 0.6%); patients remained stable for 3 years when off lithium treatment 20 times more frequently after gradual than rapid discontinuation (37% vs. 1.8%; p < .0001). Ratios of median survival times after gradual/rapid lithium discontinuation were similar for a first recurrence of mania and depression (4.4 vs. 3.4-fold), insignificantly higher (34%) with rapid or continuous cycling before lithium, and greater in Type II than Type I disorder (9.8- vs. 4.0-fold). The polarity of first off-lithium and first lifetime episodes matched in 70% of cases. CONCLUSION: These pooled results strengthen the concept or a pharmacodynamic stress factor in early relapse after stopping lithium maintenance and support the conclusion that early recurrence risk can be minimized by discontinuing maintenance treatment gradually in both Type I and II bipolar disorders.

Adult↗
PubMed1993

Seasonal mood disorders. Patterns of seasonal recurrence in mania and depression.

DSM-III-R criteria, applied retrospectively in a research-oriented psychiatric clinic, identified patients (N = 146) with a mood disorder and a seasonal pattern of recurrence (seasonal mood disorder). The seasonal mood disorder syndrome was not rare (10% of all mood disorders); diagnostic distribution was as follows: recurrent depression, 51%, and bipolar disorder, 49%, with 30% of the latter having mania (bipolar disorder type I) and 19% having hypomania (bipolar disorder type II). Most patients were women (71%); onset age averaged 29 years, with a mean of eight cycles in 12 years of illness; mean episode duration was 5.0 months. Mood disorder was found in a high proportion (68%) of the families. All but one patient followed one of two seasonal patterns in equal frequency: type A, fall-winter depression with or without spring-summer mania or hypomania; and type B, spring-summer depression with or without fall-winter mania or hypomania. Both types showed consistent times of onset and remission. These results emphasize that DSM-III-R seasonal mood disorder includes severe cases of recurrent depression and bipolar disorder and support a distinction between two seasonal subtypes.

Adult↗
PubMed1993

Outcome after rapid vs gradual discontinuation of lithium treatment in bipolar disorders.

OBJECTIVE: Withdrawal of bipolar mood disorder (BP-I) patients from prolonged, stable lithium maintenance has a high risk of early recurrence, particularly of mania. We thus compared risks of stopping lithium rapidly vs gradually. DESIGN: Outpatients undergoing clinically determined discontinuation of lithium treatment at different rates were followed up prospectively to 5 years. Risks and timing of new episodes were analyzed. PATIENTS: Subjects (N = 64) with a DSM-III-R BP disorder, previously stable on lithium monotherapy for 18 to 120 months (mean, 3.6 years) were followed up clinically after discontinuing lithium (elected in prolonged wellbeing in 67%). None was unavailable for follow-up, and subtyping (BP-I or BP-II) remained stable. RESULTS: Within 5 years, 75% had a recurrent episode; BP-I patients were 1.5-times less likely than BP-II to remain in remission. Polarity of first-recurrent and onset episodes was 80.8% concordant. Overall risk of a new episode of mania was significantly greater after rapid (< 2) than gradual (2 to 4 weeks discontinuation (5-year hazard ratio = 2.8); the difference in risk of depression was even greater hazard ratio = 5.4). Recurrence rate was more elevated within months of rapid discontinuation (12-month hazard ratio = 5.4). Recurrence rate was more elevated within months of rapid discontinuation (12-month hazard ratio = 4.3) than at later times (2 to 5 years), when courses of "survival" over time were nearly parallel in both discontinuation groups. CONCLUSIONS: Risk of early recurrence of BP disorder following discontinuation of lithium maintenance is elevated, but may be both predictable (timing and polarity) and modifiable by gradual discontinuation.

Adult↗
PubMed1993

Effects of low-dose dexamethasone on sleep EEG patterns, plasma cortisol, and the TSH response to TRH in major depression.

Dexamethasone (DEX) (0.5 mg, P.O.) and placebo were administered at 2300 h in randomized design to 19 patients with major depression and the effects on the sleep electroencephalogram (EEG) were studied. In addition, the thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) and basal plasma cortisol concentrations were assessed the following morning. DEX did not affect sleep architecture or continuity variables, including rapid eye movement (REM) latency, REM activity and REM density. Similarly, DEX did not significantly influence the TSH response to TRH (delta max TSH). In contrast, plasma cortisol concentrations were significantly suppressed by DEX. The results indicate that, as opposed to higher dosages of glucocorticoids, 0.5 mg DEX had minimal effects on the sleep EEG or delta max TSH in depressed patients.

Adult↗
PubMed1992

Relationship between REM sleep latency and nocturnal cortisol concentrations in depressed patients.

Due to conflicting reports on the possible association between shortening of rapid eye movement (REM) latency and increased cortisol secretion in patients with severe depression, this study examined the relationship between REM sleep latency and nocturnal cortisol concentration in 12 outpatients with major depression. The results showed a significant inverse correlation (r = -0.71, P < 0.01) between REM sleep latency and mean (23.00 hours-03.00 hours) plasma cortisol concentration. Age and severity of depression did not contribute to the inverse relationship. REM activity and density during the first REM period showed no significant correlations with the cortisol measures. A review of the literature suggests that this relationship might be unique to subjects with major depression, and again raises the possibility that these biological disruptions may have a common neurochemical basis.

Journal Article↗