Vasilios G. Masdrakis

Pregabalin in the discontinuation of long-term benzodiazepines' use†

Tolerance, dependence, and adverse effects on cognitive functions are well‐known consequences of long‐term use of benzodiazepines (BDZ), especially at high doses, raising thorny therapeutic problems in their discontinuation. One promising pharmacological agent in BDZ discontinuation might be the newer anti‐epileptic pregabalin, already successfully tested in the treatment of anxiety disorders.

Testosterone and dehydroepiandrosterone sulfate in female anxious and non-anxious major depression

Abstract Objectives. Major Depression with severe anxiety has been proposed as a distinct clinical variant of Major Depressive Disorder (MDD). This proposal invites the investigation of the differential biological correlates of the anxious versus non-anxious MDD. One such research area might be their possible differential associations with androgens. Methods. Plasma total testosterone and dehydroepiandrosterone were assessed in adequately matched female inpatients with anxious MDD, non-anxious MDD and normal controls. Results. Androgen levels were significantly lower in both patient groups compared to those of controls. Moreover, they were significantly lower in anxious MDD patients compared to those of their non-anxious MDD counterparts. The limitations of this study were cross-sectional design of the study, the small sample size of the study sample and the outpatient status of the control group. In addition, free testosterone levels were not measured. Conclusions. Our findings indicate that female major depression is associated with lower androgen levels, a deficiency aggravated by the severity of their concomitant anxiety.

Levetiracetam in the treatment of antipsychotics-resistant Tourette syndrome

Levetiracetam, an anti-epileptic agent that enhances GABAergic neurotransmission, is one of the newest alternative treatments of Tourette syndrome (TS). We present the case of a 23-year-old female patient suffering from TS since the age of 7, who exhibited poor response to a variety of agents (haloperidol, pimozide, clonidine and various adjunctive agents) and had four hospitalizations during the previous 2 years due to the deterioration of her clinical state. On her last admission, in addition to clonidine 600 µg/day (already part of her regimen for the previous 4 years), levetiracetam was prescribed, up to 2000 mg/day, progressively titrated over a 3-week period. The patient presented a significant improvement on her TS symptomatology (the score on the Yale Global Tic Severity Scale dropped from 70 at admission, to 25 five weeks later, at discharge), which was preserved during the subsequent 4 months, without any serious side-effect.

Cognitive effects of pregabalin in the treatment of long-term benzodiazepine-use and dependence.

Long‐term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long‐term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long‐term BDZ use and dependence with PGB.

Bilateral ankle oedema in a patient taking escitalopram

Escitalopram (ESC) is the S-isomer of the racemic compound citalopram, and has been shown to be an efficacious treatment for major depressive disorder. Several studies or case reports are available describing its side effects, none of which however refer to its potential to induce ankle oedema. We report the case of a 69-year-old female depressed patient who, after approximately 1 month of therapy with ESC, progressively titrated up to 30 mg/day, developed a bilateral ankle oedema, which resolved completely within the first week following its discontinuation.

Tiagabine augmentation to fluvoxamine-risperidone combination in the treatment of obsessive-compulsive disorder.

Despite the recent progress in the pharmacological treatment of obsessive-compulsive disorder (OCD) – especially with high doses of serotonin reuptake inhibitors, alone or in combination with low doses of antipsychotics – a non-negligible proportion of patients remains refractory to it. For these patients augmentation tactics with drugs from other chemical classes, including antiepileptic drugs, seems advisable. We report on the case of a female inpatient with OCD, whereby the adjunction of tiagabine, a selective GABA reuptake inhibitor at 15 mg/day, to a fluvoxamine (400 mg/day)–risperidone (1 mg/day) combination led to the patients marked improvement as reflected in the reduction by almost 47% of her score on the Yale-Brown Obsessive Compulsive Scale. With respect to tiagabines specifically anti-OCD mechanism of action, we note that enhanced inhibitory GABAergic neurotransmission slows down excitatory glutamatergic transmission in the cortico-striato-thalamic system, which presumably constitutes the core pathophysiological mechanism of OCD symptoms.

For publication: Tiagabine in the discontinuation of long-term benzodiazepine use

TOLERANCE, DEPENDENCE AND withdrawal symptoms are well-known complications of long-term benzodiazepine (BDZ) use, raising thorny problems in any attempt at their discontinuation. Among the scarce available pharmacological interventions, gradual rather than abrupt discontinuation of BDZ and use of the antiepileptic drug (AED) carbamazepine are the only successfully tested ones for their efficacy. Thus, newer innovatory treatments are clearly desirable. The recent marketing of newer AED, especially of the Selective GABA-Reuptake-Inhibitors, such as tiagabine (TGB) might offer new therapeutic options to this end. However, to the best of our knowledge, no such studies or reports are as yet available. In the following, we report precisely on such a case. This is the case of a 68-year-old female patient with a 15-year history of generalized anxiety disorder (GAD) and BDZ-dependence according to Diagnostic and Statistical Manual of Mental Disorders (text revision) criteria without any other psychiatric comorbidity, or medication. For the last five years, she was clearly abusing the BDZ bromazepam at a dosage of 75 mg/day, moreover with a notable tolerance to this drug, as attested by her high levels of anxiety despite its high dosage. This fact along with her resolution to address her BDZ-dependence motivated her hospitalization at our Department. On admission, the patient scored 39 on the Hamilton Anxiety Rating Scale (HARS). Her extensive medical and laboratory workup yielded no pathological findings. After obtaining the patient’s written informed consent, we incrementally substituted TGB up to 15 mg/day for bromazepam within one week, each day replacing 10 mg of the latter with 2 mg of the former. Dizziness, headache and sedation were the only transient side-effects of TGB, subsiding within 10 days. On discharge, four weeks later, the patient’s scores on the HARS had dropped to 22, a reduction rate by almost 44%. With respect to its mechanism of action, we should note that TGB enhances GABAergic neurotransmission through its blockade of the GABA transporter I (GAT I). Besides its indication in epilepsy, TGB has been found safe and efficacious in various anxiety disorders including GAD, panic disorder, agoraphobia and post-traumatic stress disorder. Moreover, in another recent study TGB has been found efficacious as monotherapy for major depressive disorder with anxiety. However, we should mention the possible temporal delay of TGB – one week – to bring about its anxiolytic effects. Although anecdotic and thus warranting replication in large and wellcontrolled studies, the findings of our case report suggest that TGB might be a promising new pharmacological agent in the treatment of BDZ dependence. REFERENCES

Cardiac safety of the electroconvulsive therapy-paliperidone combination: a preliminary study.

Both electroconvulsive therapy (ECT) and paliperidone (PLP) can induce, though infrequently, severe cardiac side-effects. Thus far, no studies are available on the cardiac safety of their co-administration. We report on the cardiac safety of the ECT-PLP combination in nine female inpatients who underwent this treatment modality. In a total of 83 ECT patient sessions, the ECT-PLP combination was well tolerated. No patient exhibited any noticeable prolongation of QTc interval and no adverse cardiac events, in particular arrhythmias, were noted.

P03-453 - Mental pain and suicide risk in women with major depression

Objectives Previous studies have provided evidence on the possible relationship between mental pain (psychache) and suicide. The aim of the present study was to investigate whether more intense psychache is related with higher suicide risk independently of the severity of depression. Methods Orbachs Mental Pain Scale was administered in 58 women with major depression: 24 inpatients and 34 outpatients. Severity of depressive symptoms was evaluated by the Beck Depression Inventory. Suicide Risk Scale was used for the assessment of suicide risk. Level of physical pain was measured by McGill Pain Questionnaire-Short form. Pearsons correlation was used to examine the relationship between variables and a multiple regression analysis was performed to examine the independent strength of the associations. Results Suicide risk was significantly and positively associated with the level of current psychache and the severity of depressive symptoms, and negatively with the age of onset of the illness. The levels of physical pain or worst-ever psychache were also correlated with suicide risk; however, these associations did not remain significant in the multiple regression models. Conclusions Higher levels of mental pain may be a factor of vulnerability to suicidal behaviour in major depression. Higher symptom severity and earlier onset of the illness may also contribute to suicide risk. The association between physical pain and suicide risk appears to be mediated by mental pain or other aspects of the illness.

P02-201 - Safety of the electroconvulsive therapy-paliperidone combination

Objectives Patients with psychotic or mood disorders often undergo electroconvulsive therapy (ECT) while receiving antipsychotic and/or other pharmacological agents. Paliperidone (PLP) -a benzisoxazole derivative and the principal active metabolite of risperidone- is a second-generation antipsychotic which has been developed in an osmotic controlled-release oral-delivery system. Thus the peak-through fluctuations of its concentration in plasma are minimized, with consequently decreased incidence of side-effects. To the best of our knowledge, there are, as yet, no reports on the safety of ECT-PLP co-administration. Methods Nine female inpatients suffering from affective disorders (N=7) or schizophrenia (N=2) underwent ECT while receiving PLP (3-12 mg/d). Patients’ regimen included other psychotropic medications as well (mainly antidepressants and/or antipsychotics). All patients were monitored closely for recovery time, post-ictal delirium, cardiological and EEG status for at least one hour after each ECT session. In addition to their clinical evaluation, patients’ cognitive -especially memory- functioning was regularly assessed by the Mini Mental State Examination. Overall, patients underwent 83 sessions of bilateral ECT. Results ECT-PLP combination was well tolerated and even in cases where cognitive side-effects were of moderate severity (three cases; all were also receiving venlafaxine), they were transient. Conclusions Although anecdotal and thus in need of replication in well-designed large studies, our preliminary findings suggest that ECT and PLP can be safely combined whenever both indicated.