2014, volume 30, issue 1

Original article

Efficacy of long-term lithium-treatment in bipolar disorder

Sebastian Kiwicki, Maria Chłopocka-Woźniak, Ewa Rudnicka, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2014, 1, 5–13

Objectives. The aim of the study was to investigate the efficacy of long-term lithium administration in a large group of patients with bipolar disorder (BP) and to define factors associated with the efficacy of lithium treatment.
Material and methods. The study included 111 patients (76 women, 35 men), aged 34-85 (mean age 61 years) receiving lithium for 5-39 years (mean length 18 years). Lithium efficacy was assessed using a three-step scale identifying Excellent Responders (ER), Partial Responders (PR) and Non-Responders (NR), as well as the Alda Scale rating lithium efficacy within the range of 0-10. Various clinical factors that can be linked with lithium efficacy were also analysed, including age at onset of the illness, polarity of the first episode, age at the first occurrence of elevated or depressed mood, number of affective episodes preceding lithium treatment, duration of the illness prior to lithium treatment, type of BP (I or II), family history of affective illness, comorbidity of anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, alcohol and medication abuse/dependence, suicide attempts preceding lithium therapy and the duration of lithium treatment.
Results. Among the patients studied, 27% met the criteria for ER, 63% for PR and 10% for NR. The mean score on the Alda scale was 6.6±2.5. A better effect of lithium prophylaxis was shown in patients with a later onset of the illness, without a family history of affective illness, having family members who receive lithium, in women with comorbid anxiety disorder and in men without alcohol abuse/dependence.
Conclusions. There are no recurrences of BP in about 30% of patients in long-term lithium treatment, independently of the duration of lithium administration. Also, in the present study, several other factors were identified connected with lithium efficacy.

Original article

The concentration of homocysteine and treatment of depression in affective disorders

Agnieszka Permoda-Osip, Jolanta Dorszewska, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2014, 1, 15–20

Background: The aim of the study was to measure the level of HCY, vitamin B12 and folic acid, in depression in the course of affective disorders as well as HCY level during remission after pharmacological treatment.
Methods: One-hundred and thirty-three patients (29 male, 106 female), mean age 51±14 years, with depression in the course of bipolar I (37 patients), bipolar II (79 patients) and unipolar (17 patients) mood disorder were studied. The duration of illness was 8.2± years, and duration of a depressive episode was 4.6±1.8 months. The intensity of depression, as measured by the 17-item Hamilton Depression Rating Scale (HDRS), was 19.6±9.5 points. The second measurement of HCY was carried out after the treatment with an antidepressant or/and mood-stabilizing drugs, with depression intensity of ≤7 points. Hyperhomocysteinemia (HHCY) was defined as HCY level >15 μM/l.
Results: During a depressive episode, the mean HCY concentration was 14.0±8.2 mM/l, of vitamin B12 342±145 pg/ml, and folic acid 5.79±2.96 ng/ml. Significant negative correlation was found between the levels of HCY and of both vitamins. HHCY before treatment was observed in 38% of patients, significantly more often in men (62%) than in women (32%). During remission, the mean HCY concentration was 13.0±7.5 mM/l, (significant difference in bipolar II) and the percentage of patients with HHCY significantly decreased (23% of patients 38% male, 19% female).
Conclusions: These results point to a significant frequency of HHCY, especially in men, during depression in the course of affective disorders as well as its marked decrease after the treatment. They also confirm a correlation between an increased concentration of HCY and lower level of vitamin B12 and folic acid during a depressive episode. However, further studies are needed to better define a pathogenic role of HCY in affective disorders.

Original article

Hypercalcaemia and hyperparathyroidism in bipolar patients on long-term lithium treatment

Maria Abramowicz, Maria Chłopocka-Woźniak, Agnieszka Kraszewska, Stanisław Czekalski, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2014, 1, 21–27

Objectives. The aim of the study was to assess the effect of chronic lithium treatment on serum calcium concentration and the parathyroid function when hypercalcemia was detected in bipolar patients, and to compare the results with age and sex matched patients who had never been exposed to lithium.
Material and methods. The study comprised 90 patients aged 60±10 years who received lithium for mean 16±10 years and 30 patients, aged 56±12 years, never exposed to lithium. The serum calcium levels were measured in all patients. In lithium-treated subjects, the parameters of kidney function and novel biomarkers of kidney injury were assessed. Serum parathyroid hormone levels were assessed in lithium- treated patients with hypercalcemia. Abdominal USG examinations were also carried out.
Results. Patients who received lithium had significantly higher mean serum calcium concentrations, compared with the control group. Hypercalcemia was found in 10% of long-term lithium-treated patients, more frequently than in the control group. The prevalence of hypercalcemia was higher among lithium-treated women than in men. In lithium-treated patients no association between serum calcium levels and age or duration of lithium treatment were found. Hyperparathyroidism was found in 3 out of 9 lithium-treated patients with hypercalcemia. The incidence of nephrolithiasis was more frequent in lithium-treated patients.
Conclusions. The results of the study confirm that long-term lithium treatment is associated with irregularities in calcium metabolism and parathyroid function and suggest, similarly to the results obtained by other researchers, that monitoring of serum calcium concentrations in lithium- treated patients is necessary.

Review article

Bleeding complications in the course of treatment with antidepressants in elderly patients

Adam Wysokiński, Tomasz Sobów
Farmakoterapia w Psychiatrii i Neurologii, 2014, 1, 29–35

Literature review on bleeding complications in the course of treatment with antidepressants is presented. We have focused on elderly patients since they are in the high risk group. Incidence of bleeding complications, their causal relations with antidepressants, possible risk factors and methods of prevention are discussed. The data indicate that treatment with antidepressants of serotonergic mechanism of action is associated with an increased risk of bleeding complications, which are most frequent in patients treated with SSRIs, venlafaxine, trazodone and tricyclic antidepressants. The lowest risk is associated with agomelatine, bupropion, reboxetine and mirtazapine. Due to possible serious consequences of bleeding complications, clinicians should consider individual risk factors when choosing antidepressive treatment, particularly in elderly patients.

Case report

Dependence on tianeptine: case report and review of the literature

Ewa Dopierała, Ewa Ferensztajn, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2014, 1, 37–42

Tianeptine is an atypical tricyclic antidepressant, the efficacy of which in the treatment of depressive episodes, dysthymia, adjustment disorder, and anxiety is comparable with the selective serotonin reuptake inhibitors (SSRI). The main mechanism of tianeptine’s action is based on the modulation of stress axis activity and increase of serotonin reuptake with additional pro-dopaminergic effects. Despite the many advantages, we find more and more reported cases of addiction to tianeptine, due to its psychostimulant properties and lack of side effects. It is reported in the literature that the dependence index (the so-called DSI – doctor shopping index) for tianeptine is at a level similar to benzodiazepines. We present the case of a 43 year-old woman with bipolar disorder and multiple drug abuse, who took tianeptine up to the dosage of 1125 mg/day (90 tablets). Treatment with valproic acid, bupropion and sertraline resulted in a gradual improvement of her mental condition, enabling her to function satisfactorily day to day.

Case report

Use of tetrabenazine for treatment-induced tardive dyskinesia – two case reports

Adam Wysokiński, Radosław Magierski, Iwona Kłoszewska
Farmakoterapia w Psychiatrii i Neurologii, 2014, 1, 43–48

Tardive dyskinesia is a cluster of involuntary, irregular, hyperkinetic movements involving different muscle groups. Tardive dyskinesia, as a side effect, occurs in 15-20% of patients treated with antipsychotics. Complete remission is rare and occurs in 2% of patients after the treatment is discontinued. In case of tardive dyskinesia, switching to a second-generation antipsychotic and reduction of a dose over a few months should be considered. There have been also attempts to treat tardive dyskinesia with benzodiazepines, vitamin E, botulinum toxin and ondansetron. Tetrabenazine is a moderen and expensive, pharmacological option which is currently not registered in Poland. The course and effects of treatment with tetrabenazine in two patients with tardive dyskinesias are described. On the basis of our experience, gained during the tetrabenazine research program, we believe that the use of this drug should be limited to patients who are in stable mental condition, without any symptoms of depression or active psychotic symptoms. In our opinion, the presence of suicidal tendencies or thoughts and history of neuroleptic malignant syndrome are definite contraindications.