24-hour lithium concentration in human brain studied by Li-7 magnetic resonance spectroscopy.

Brain and serum lithium concentrations were measured every second hour during a 24-hr period following lithium intake, and again 48-hr later in two normal subjects in steady state lithium treatment receiving lithium carbonate (Priadel Synthelabo) once every evening. The brain-lithium concentration was measured by 7Li magnetic resonance spectroscopy (MRS). The brain lithium level was found to undulate in a peak-trough pattern that followed the serum lithium profile, although in an attenuated form. The brain/serum lithium concentration ratio varied considerably during the 48-hr period, ranging from 0.5 to 1.3, but the ratio was independent of the serum-lithium concentration. The median half-life for lithium was 28 hr in the brain, and 16 hr in serum. The brain lithium concentration in the morning was about 75% of the clinically relevant standard 12-hr serum lithium concentration. The finding that brain lithium undulates during the day means that MRS measurements of brain lithium can only be compared if carried out under standard conditions that include a fixed interval following lithium intake and an identical treatment regimen.

Twelve-hour brain lithium concentration in lithium maintenance treatment of manic-depressive disorder: daily versus alternate-day dosing schedule.

The 12-h brain lithium concentration was measured by lithium-7 magnetic resonance spectroscopy in ten manic-depressive patients receiving daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 800 mg in the daily treatment group and 1200 mg in the alternate-day group. Median 12-h serum lithium concentration in the two groups was 0.86 mmol l-1 and 0.55 mmol l-1, respectively, while the corresponding concentration in brain was 0.67 mmol l-1 and 0.52 mmol l-1, respectively. The 12-h brain lithium concentration was independent of lithium dosing schedule (multiple linear regression), but correlated significantly with the 12-h serum lithium concentration (P = 0.003; B = 0.53, 95% c.l. 0.24-0.82; beta = 0.83). Thus at identical 12-h serum lithium concentrations the 12-h brain lithium concentration is similar with both treatment regimes. As the risk of manic-depressive relapse during alternate-day lithium treatment is in our experience 3-fold greater than with daily treatment (at similar mean 12-h serum lithium concentration), the findings suggest that the difference in the prophylactic efficacy of the two dosing schedules is unrelated to differences in the 12-h brain lithium concentration.

Urinary excretion of albumin and transferrin in lithium maintenance treatment: daily versus alternate-day lithium dosing schedule.

Urinary excretion of albumin and transferrin was determined by means of sensitive immunochemical methods in 40 manic-depressive patients prior to and following 6 months of daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 700 mg in the daily treatment group and 1200 mg in the alternate-day group, the corresponding median 12-h serum lithium concentration being 0.6 mmol l-1 and 0.7 mmol l-1, respectively. Urinary excretion of albumin and transferrin was significantly elevated in the lithium-treated patients as compared to a control group (Mann-Whitney). The change in urinary albumin:creatinine and transferrin:creatinine ratios between allocation and 6 months of treatment did not correlate significantly with the lithium dosing schedule (multiple linear regression), but did correlate with total lithium carbonate dose. In conclusion, the study provides no evidence of any difference in glomerular function (permeability) in the daily and alternate-day lithium dosing schedules, and lends no support to the hypothesis that alternate-day treatment diminishes the effect of lithium on renal function.

Double-blind comparison of the side-effect profiles of daily versus alternate-day dosing schedules in lithium maintenance treatment of manic-depressive disorder.

The side-effect profiles of daily vs. alternate-day lithium carbonate dosing schedule were compared in a double-blind study of 50 manic-depressive patients. Following a 3-month period on daily lithium maintenance treatment the patients were randomly allocated to daily or alternate-day lithium dosing aiming at maintaining the same 12-h serum concentration as prior to allocation (median 0.7 mmol/l). The daily and alternate-day median lithium doses were 700 mg and 1200 mg, respectively. There was no significant correlation between changes in the side-effect scores on the UKU side-effect rating scale and lithium dosing schedule (ordinal logistic regression), although analysis revealed a trend in favour of alternate-day dosing with respect to polyuria/polydipsia and diarrhoea (loose stool). The study thus lends no support to the hypothesis that lithium-related side-effects can be diminished by extending the interval between lithium doses from 1 to 2 days.

An open, noncomparative study of amoxapine in borderline disorders.

Five patients with borderline personality disorder (BPD) and 5 patients with schizotypal personality disorder (SPD) completed at least 3 weeks of treatment with amoxapine. The patients fulfilled DSM-III criteria for borderline disorders and scored 7 points or more in Gunderson's Diagnostic Interview for Borderlines (DIB). The final median medication in patients with BPD was 200 mg amoxapine/day and 42 mg oxazepam/day. Duration of treatment averaged 28 days. In patients with SPD the corresponding figures were 250 mg amoxapine/day, 36 mg oxazepam/day and 39 days. The study suggests that amoxapine improves schizophrenic-like and depressive symptoms in patients with schizotypal personality disorders (SPD). No effect could be shown in patients with borderline personality disorders (BPD).

Prolactin responses to thyrotropin-releasing hormone in multi-infarct dementia and senile dementia of the Alzheimer type.

The serum prolactin (PRL) responses to stimulation with thyrotropin-releasing hormone (TRH) (500 micrograms Protirelin) were compared in 14 patients with multi-infarct dementia (MID) and 10 patients with senile dementia of the Alzheimer type (SDAT). Between the MID and the SDAT patients, there were no statistically significant differences in the median serum PRL concentrations, median changes in serum PRL concentrations or median proportional changes in serum PRL concentrations. Further, the serum PRL responses did not correlate with the GBS scale scores (degrees of dementia) or the GBS subscale scores (clinical profiles, including motor functioning, emotional functioning and intellectual functioning). In conclusion, the study does not support the hypothesis that serum PRL responses to TRH stimulation are of diagnostic value in differentiating between MID and SDAT.

Urinary excretion of albumin and retinol-binding protein in lithium-treated patients.

Urinary excretion of albumin and retinol-binding protein was measured by means of sensitive and specific immunochemical methods in a transverse study of 20 lithium-treated patients and 24 apparently healthy individuals. Albumin creatinine clearance ratios were significantly higher in the lithium-treated patients, which may indicate glomerular lesions. Microalbuminuria correlated highly to duration of lithium therapy. No significant difference between the retinol-binding protein creatinine clearance ratios in the two groups could be shown. This suggests that the catabolism of low-molecular-mass proteins in the proximal tubules was normal.

Fluvoxamine in the treatment of demented elderly patients: a double-blind, placebo-controlled study.

The efficacy of fluvoxamine on cognitive functioning and behavioral changes was evaluated in a double-blind, placebo-controlled study of 46 elderly demented patients. The patients had a DSM-III diagnosis of primary degenerative dementia or multi-infarct dementia and were aged greater than or equal to 65 years. Twenty-two patients were given 150 mg fluvoxamine per day and 24 received placebo tablets; 14 and 15 patients, respectively, completed 6 weeks of treatment. Within treatments, there were no significant changes in median scores on neuropsychological tests (picture recall and recognition, trail making and finger tapping) or the GBS scale scores (degrees of dementia) or GBS subscale score (clinical profiles, including symptoms common in dementia, motor, emotional and intellectual functioning). Between treatments, the median changes in psychometric test scores did not differ significantly. However, within and between treatments, there were trends favoring fluvoxamine on symptoms common in dementia (confusion, irritability, anxiety, fear-panic, mood level and restlessness). In conclusion, the study does not support the hypothesis that fluvoxamine improves cognitive functioning or behavioral changes in elderly dementia patients.

Urinary excretion of albumin and retinol-binding protein in lithium-treated patients: a longitudinal study.

The urinary excretion of albumin and retinol-binding protein was determined by means of sensitive immunochemical methods in a 2-year longitudinal study of 22 lithium-treated patients. During lithium treatment, there were no significant changes in the median albumin:creatinine ratios or retinol-binding protein:creatinine ratios. However, the median albumin:creatinine ratios were significantly higher in lithium-treated patients than in 22 normal subjects, which indicates that glomerular permeability is increased; no correlation with serum lithium level or duration of lithium treatment could be shown. In patients treated with slow-release tablets, the urinary excretion of albumin was significantly higher after 2 years than in patients given lithium carbonate. The median retinol-binding protein:creatinine ratios did not differ significantly between lithium-treated patients and normal subjects, suggesting that lithium does not affect the catabolism of low-molecular-weight proteins in the proximal tubules. In conclusion, the study supports the hypothesis that lithium treatment produces a small but significant and nonprogressive elevation of the urinary excretion of albumin.

The GBS scale in multi-infarct dementia and senile dementia of Alzheimer type.

The GBS profile was assessed for 39 patients with multi-infarct dementia (MID) and 34 patients with senile dementia of Alzheimer type (SDAT). The MID patients fulfilled the DSM-III criteria for multi-infarct dementia and had a score of 7 points or more on the Hachinski Ischemic Scale (HIS) and a score of 4 points or less on the Gustafson/Nilsson Alzheimer Scale (GNAS). The SDAT patients fulfilled DSM-III criteria for primary degenerative dementia and had a score of 5 points or more on the GNAS and a score of 6 points or less on the HIS. The total GBS score, the GBS subscale and relative subscale scores for intellectual functioning were significantly higher in patients with SDAT as compared with patients with MID. However, these subscale scores were considerably dispersed and nearly totally overlapping between patients with MID and SDAT, which implicates that the discriminative value is minimal. The validity between the GBS versus HIS and between the GBS versus GNAS was divergent, suggesting that the GBS scale has its own unique validity. In conclusion, the study does not support the hypothesis that the GBS profile may be of diagnostic value in clinical differentiation between multi-infarct dementia (MID) and senile dementia of Alzheimer type (SDAT).

Lithium prophylaxis of manic-depressive disorder: daily lithium dosing schedule versus every second day.

The prophylactic efficacy of lithium carbonate given every second day versus daily intake was compared in a double-blind study including 50 manic-depressive patients. The patients met the DSM-III-R criteria for bipolar disorder or depressive disorder; according to ICD-8 the patients fulfilled criteria for manic-depressive disorder: All patients had experienced at least 3 episodes of mania or major depression, and all had been euthymic for at least 4 months. The median doses of lithium carbonate given were 800 mg/day or 1200 mg/every second day corresponding to median 12-h serum lithium concentrations of 0.6 mmol/l or 0.7 mmol/l, respectively. Manic or depressive relapse was defined as DSM-III-R criteria for mania or major depression, and a score > or = 10 on the Bech-Rafaelsen Mania Scale or the Bech-Rafaelsen Melancholia Scale, respectively. The two treatment schedules were allocated at random. Using the Cox proportional hazard model for statistical analysis, the lithium dosing schedule of every second day did not maintain its prophylactic efficacy against recurrent episodes of manic-depressive disorder. The risk of relapse increased 3 times when the interval between intake of lithium was extended from 1 to 2 days.