Lefteris Lykouras

Obsessive-compulsive symptoms induced by atypical antipsychotics. A review of the reported cases.

Atypical antipsychotics (APs) are now widely in use in clinical practice. They exert a beneficial effect in patients with schizophrenic disorders, including cases resistant to traditional APs and negative symptoms. They have also enhanced the ratio of therapeutic efficacy to adverse effects. Atypical APs, mainly risperidone and olanzapine, have been used as adjunctive treatment in (selective) serotonin reuptake inhibitor [(S)SRI]-refractory cases with obsessive symptoms. However, de novo emergence or exacerbation of obsessive-compulsive (OC) symptoms during treatment with clozapine, risperidone, olanzapine and quetiapine has been described in the literature. The reported cases and the possible pathogenetic mechanisms involved in their occurrence are discussed and reviewed.

Switch from neuroleptics to clozapine does not influence pituitary–gonadal axis hormone levels in male schizophrenic patients

Hypothalamic dopaminergic and serotonergic inputs participate in the regulation of pituitary hormones, and drugs that block central dopamine and serotonin receptors are expected to influence the hypothalamus-pituitary-gonadal (HPG) and -adrenal (HPA) axes. In schizophrenic patients, the switch from neuroleptics to clozapine influences prolactin and cortisol secretion, but there is no information on possible changes on HPG-axis hormones. We measured the plasma levels of testosterone (TST), LH, FSH, as well as of prolactin (PRL) and cortisol (CORT), in a group of male patients with schizophrenia during treatment with classical neuroleptics with no satisfactory therapeutic response (31 pts, age 30.3+/-8.5, range 18-50), and 6 weeks later, after switch to treatment with clozapine (CLZ) in doses from 100 to 600 mg daily (mean 328 mg). Psychopathology was assessed using the Brief Psychiatric Rating Scale. The hormone levels were also compared to those of a control group of 38 healthy males. Treatment with CLZ resulted in a reduction in the BPRS score by 30% in the mean. Plasma PRL was reduced from 39.9+/-26.1 to 8.3+/-5.0 ng/ml (P<0.001), CORT from 150+/-42 to 118+/-39 ng/ml (P < 0.003), while LH, FSH, and TST remained unaltered. Compared to healthy controls, patients had higher PRL and CORT levels while on neuroleptics, and no significant differences to any of the estimated hormones, after switch to clozapine. The results show that switching from classical neuroleptics to treatment with clozapine does not have any substantial effect on the HPG-axis hormone plasma levels, although it reduces substantially the levels of prolactin and cortisol.

Olanzapine and obsessive-compulsive symptoms

Clozapine and risperidone have been implicated in the development of obsessive-compulsive symptoms. We present three cases in which olanzapine caused a significant exacerbation of obsessive-compulsive symptoms in schizophrenia (two cases) and obsessive-compulsive disorder (one case).

Neuropsychological and hypothalamic–pituitary-axis function in female patients with melancholic and non-melancholic depression

BackgroundExecutive function deficits in depression implicate involvement of frontal–striatal circuits. However, studies of hypothalamic–pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal–hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits.MethodForty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex- age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/ extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured.ResultsThe MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group.ConclusionsMDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

Neuroendocrine responsivities of the pituitary dopamine system in male schizophrenic patients during treatment with clozapine, olanzapine, risperidone, sulpiride, or haloperidol.

Background Atypical antipsychotic drugs, in clinical doses, occupy 5-HT2 receptors near saturation, while D2 dopamine receptors, assessed usually in striatum by SPECT or PET methods, are occupied to different degrees. We hypothesized that these differences in D2 receptor occupancies may also be evaluated by a neuroendocrine approach, namely by measuring the plasma prolactin responses to i. m. administered haloperidol, since the expected elevations depend mainly on the free remaining D2 receptors in the tuberoinfundibular tract. Methods We measured the plasma prolactin levels at 0, 30, 60, 90, and 120 minutes after administration of 5 mg haloperidol i. m. in six groups of male patients with schizophrenia: a) 33 patients in a drug-free state, b) 15 patients on treatment with clozapine (range 200–600 mg/day), c) 15 patients on olanzapine (10–30 mg/day), d) 14 patients on risperidone (8–16 mg/day), e) 23 patients on haloperidol (10–40 mg/day), f) 14 patients on sulpiride (600–1600 mg/day). Data were also obtained from a group of 14 healthy male control subjects. The differences in baseline prolactin levels and in the responses to acute haloperidol of the seven groups were compared. Results The baseline prolactin levels did not differ significantly in the groups of controls (8.3±3.8 ng/ml), drug-free patients (8.0±3.6) and patients treated with clozapine (7.7±3.8), they were moderately elevated in patients treated with olanzapine (16.8±8.9), elevated in patients on haloperidol (34.4±17.3), and they were even higher in the groups of patients treated with risperidone (54.9±22.4) or sulpiride (58.8±27.0). All groups of patients gave attenuated prolactin responses to i. m. haloperidol compared to healthy controls. During treatment with haloperidol, risperidone, or sulpiride, no significant prolactin increases after i. m. haloperidol were observed. The group treated with olanzapine gave significant prolactin increases, which were lower than those obtained in the group of patients treated with clozapine, who gave responses similar to that of the drug-free patients. Conclusions Plasma prolactin levels and responses to i. m. haloperidol of patients on treatment with antipsychotic drugs, reflect the prolactin release potencies of the drugs, which are related, but not restricted, to their affinities to D2 dopamine receptors. According to the prolactin baseline levels and responses to i. m. haloperidol, the drugs of this study can be categorized for their potency to the pituitary dopamine system that controls prolactin release, as follows: sulpiride > risperidone > haloperidol > olanzapine > clozapine. This categorization is similar to that obtained by binding studies in striatal D2 dopamine receptors using brain imaging techniques.

Association of Serum Brain-Derived Neurotrophic Factor and Duration of Untreated Psychosis in First-Episode Patients with Schizophrenia

Background/Aims: The brain-derived neurotrophic factor (BDNF) levels in serum and the central nervous system are altered in patients with schizophrenia, suggesting that changes in the expression of BDNF might contribute to the disease pathophysiology. Long duration of untreated psychosis (DUP) has been associated with poorer prognosis in patients with schizophrenia. Such a relationship of untreated psychosis to outcome may indicate a neurodegenerative process and may have important implications for understanding the pathophysiology of schizophrenia. Methods: In this study, we investigated the association between serum BDNF levels and DUP in a sample of drug-naïve patients in their first episode of schizophrenia (FEP). We investigated serum BDNF levels in a sample of 37 drug-naïve FEP patients and 21 matched healthy subjects. Results: The serum BDNF level in the sample of FEP was significantly reduced compared to the healthy subjects (18.87 ± 8.23 vs. 29.2 ± 7.73 ng/ml, t = 4.76, d.f. = 57, p = 0.01). A negative correlation was found between serum BDNF levels and DUP in the group of patients (r = –0.346, p = 0.036). Conclusions: Our findings indicate that low serum BDNF levels at the onset of schizophrenia were associated with a long DUP and this could reflect an acute neurodegenerative reaction during the untreated phase of psychosis.

Psychological Profile of Obese Patients

Nowadays obesity is recognized to be one of the greatest public health problems worldwide. There is no indication that the huge increase in obesity seen the last decades is declining. The examination of psychological aspects of persons with morbid obesity is essential. Identification of the psychological factors associated with weight loss expands our knowledge about behaviors which are crucial in order to avoid failures in treatment. Most information on this is obtained preoperatively. Although there is no single personality type characteristic of the morbidly obese, they differ from the general population as their self-esteem and impulse control is lower. They have passive dependent and passive aggressive personality traits, as well as a trend for somatization and problem denial. Their thinking is usually dichotomous and catastrophic. Obese patients also show low cooperativeness and fail to see the self as autonomous and integrated. In the morbidly obese before undergoing surgical treatment, unusual prevalence of psychopathology, namely depression and anxiety disorders, is observed. They are subject to prejudice and discrimination and should be treated with concern to help alleviate their feelings of rejection and guilt. Information on the psychological profile of obese persons is limited. Future studies are warranted, since there is a pressured need for these people to built cognitive skills and control their body weight.

Factors affecting hospital stay in psychiatric patients: the role of active comorbidity

BackgroundResearch on length of stay (LOS) of psychiatric inpatients is an under-investigated issue. In this naturalistic study factors which affect LOS of two groups of patients were investigated, focusing on the impact on LOS of medical comorbidity severe enough to require referral.MethodsActive medical comorbidity was quantified using referral as the criterion. The study sample consisted of 200 inpatients with the diagnosis of schizophrenia and 228 inpatients suffering from bipolar disorder (type I or II). Jonckheere and Mann–Whitney tests were used to estimate the influence of referrals on LOS, and regression analyses isolated variables associated with LOS separately for each group.ResultsHalf of the patients needed one or more referrals for a non-psychiatric problem. The most common medical condition of patients with bipolar disorder was arterial hypertension. Inpatients with schizophrenia suffered mostly from an endocrine/metabolic disease - 12% of referrals were for Hashimoto’s thyroiditis. A positive linear trend was found between LOS and number of referrals; the effect was greater for schizophrenia patients. The effect of referrals on LOS was verified by regression in both groups. Overall, referred patients showed greater improvement in GAF compared to controls.ConclusionsTo our knowledge this was the first study to investigate physical comorbidity in psychiatric inpatients using the criterion of referral to medical subspecialties. Comorbidity severe enough to warrant referral is a significant determinant of hospital stay. This insight may prove useful in health care planning. The results show lack of effective community care in the case of schizophrenia and negative symptoms may be the cause of this. Our findings call for more attention to be paid to the general medical needs of inpatients with severe mental health and concurrent severe medical comorbidity.

The Alcohol Use Disorders Identification Test (AUDIT): reliability and validity of the Greek version

BackgroundProblems associated with alcohol abuse are recognised by the World Health Organization as a major health issue, which according to most recent estimations is responsible for 1.4% of the total world burden of morbidity and has been proven to increase mortality risk by 50%. Because of the size and severity of the problem, early detection is very important. This requires easy to use and specific tools. One of these is the Alcohol Use Disorders Identification Test (AUDIT).AimThis study aims to standardise the questionnaire in a Greek population.MethodsAUDIT was translated and back-translated from its original language by two English-speaking psychiatrists. The tool contains 10 questions. A score ≥ 11 is an indication of serious abuse/dependence. In the study, 218 subjects took part: 128 were males and 90 females. The average age was 40.71 years (± 11.34). From the 218 individuals, 109 (75 male, 34 female) fulfilled the criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), and presented requesting admission; 109 subjects (53 male, 56 female) were healthy controls.ResultsInternal reliability (Cronbach α) was 0.80 for the controls and 0.80 for the alcohol-dependent individuals. Controls had significantly lower average scores (t test P < 0.001) when compared to the alcoholics. The questionnaires sensitivity for scores >8 was 0.98 and its specificity was 0.94 for the same score. For the alcohol-dependent sample 3% scored as false negatives and from the control group 1.8% scored false positives. In the alcohol-dependent sample there was no difference between males and females in their average scores (t test P > 0.05).ConclusionThe Greek version of AUDIT has increased internal reliability and validity. It detects 97% of the alcohol-dependent individuals and has a high sensitivity and specificity. AUDIT is easy to use, quick and reliable and can be very useful in detection alcohol problems in sensitive populations.

Psychotic (delusional) major depression in the elderly and suicidal behaviour

BACKGROUND It has been established that depressed patients manifest a higher risk of committing suicide. The role of delusional experiences accompanying depressive symptomatology as a risk factor for suicidal behaviour has been investigated but the results are inconsistent. METHOD In the present study, 40 elderly depressed inpatients with psychotic features (DSM-IV criteria) were compared to 64 elderly depressed patients without such features in terms of suicide attempts. RESULTS The results of univariate and multivariate analyses were negative: Psychotic and nonpsychotic depressed patients did not differ with respect to attempted suicide. CONCLUSION The results of the present study support the notion that psychotic features do not increase the risk for the elderly depressed patients to attempt suicide.