CLOZAPINE: PROMISING TREATMENT FOR SUICIDALITY IN BIPOLAR DISORDER

Bipolar disorder is associated with the highest risk of completed suicide of all mental disorders. The suicide mortality of people with bipolar disorder is approximately 25 times higher than the general population. No approved pharmacological strategies for suicidality in bipolar disorder have been introduced so far. There is evidence for anti-suicidal effect of clozapine in schizophrenia. Clozapine with its unique pharmacology, anti-aggressive and anti-impulsive properties is potentially an effective strategy for suicidality in bipolar disorder

SYMPTOM FREQUENCY CHARACTERISTICS OF THE HAMILTON DEPRESSION RATING SCALE OF MAJOR DEPRESSIVE DISORDER IN EPILEPSY

Background: Depressive disorders are common among patients with epilepsy (PWE). The aim of this study was to explore symptom frequencies of 17-item Hamilton Depression Rating Scale (HDRS-17) and recognize the clinical characteristics of Major Depressive Disorder in PWE. Subjects and methods: A sample of 40 adults outpatients with epilepsy and depression was diagnosed using SCID-I for DSM-IVTR and HDRS-17. The total HDRS-17 score was analysed followed by the exploratory analysis based on the hierarchical model. Results: The frequencies of HDRS-17 items varied widely in this study. Insomnia related items and general somatic symptoms items as well as insomnia and somatic factors exhibited constant and higher frequency. Feeling guilty, suicide, psychomotor retardation and depressed mood showed relatively lower frequencies. Other symptoms had variable frequencies across the study population. Conclusions: Depressive disorders are common among PWE. In the study group insomnia and somatic symptoms displayed highest values which could represent atypical clinical features of mood disorders in PWE. There is a need for more studies with a use of standardized approach to the problem

SHORT-TERM KETAMINE ADMINISTRATION IN TREATMENT-RESISTANT DEPRESSION: FOCUS ON CARDIOVASCULAR SAFETY

Ketamine is an anaesthetic and analgesic agent that demonstrates the antidepressive effect in major depression. Several administrations routes, dosing schemas and esketamine are investigated in basic and clinical research with particular focus on treatment-resistant depression (TRD) where drug demonstrates its efficacy where very limited alternatives are available. The majority of ketamine studies in TRD treatment reported no serious adverse events regardless the administration route or regimen. However, the most commonly observed adverse events following ketamine administration in antidepressive doses include general, psychotomimetic, dissociative and hemodynamic ones. The side effects are mild or moderate, well-tolerated and transient. This paper discusses the risks regarding cardiovascular safety in MDD patients in short-term ketamine administration with particular focus on the effect on blood pressure and adverse drug reactions mitigation measures. The increase in systolic (SBP) and diastolic (DBP) blood pressure is dose-dependent and begins shortly after administration peaking at around 30 to 50 minutes with SBP and DBP rise from 10% to 50% above predose values and resolving at approximately 2 to 4 hours after the dose administration. These changes generally are primarily asymptomatic. The elevations in SBP and DBP are observed on each dosing day with multiple administration schema. The treatment with ketamine and esketamine is contradicted in subjects at risk of an increase in blood pressure or intracranial pressure. The current evidence indicates the blood pressure should be assessed prior to dosing with ketamine and hypertensive individuals shall receive effective lifestyle/pharmacologic management prior to treatment. Blood pressure should be monitored after dose administration until blood pressure returns to acceptable levels. If blood pressure remains elevated acute blood pressure management shall be delivered. In patients experiencing symptoms of hypertensive crisis immediate emergency care must be provided. The unmet need for improved pharmacotherapies for TRD means the use of ketamine and esketamine is warranted therapeutic option in patients who fail to achieve a sustained remission of depressive symptoms with drugs with monoamine-based mechanisms of action. Adequate safety measures must be applied when using ketamine/esketamine in TRD subjects with particular focus on somatic comorbidities as the transient drug effect on cardiovascular system is demonstrated and of clinical significance

BENZODIAZEPINES IN COMBINATION WITH ANTIPSYCHOTIC DRUGS FOR SCHIZOPHRENIA: GABA-ERGIC TARGETED THERAPY

Antipsychotics are a key intervention strategy in pharmacotherapy of schizophrenia. However, benzodiazepines are often prescribed to control sleep disturbances, anxiety or behavioural disinhibition. There is clinical evidence for the beneficial effect of the combined treatment of antipsychotics and benzodiazepines resulting in more favorable treatment outcome in schizophrenia with regard to positive and negative symptoms. This clinical phenomenon seems to be associated with the GABA-ergic activit ythat is believed to be disrupted in the schizophrenia and direct benzodiazepines effect on GABA-A receptors. In the brain there are both excitatory and inhibitory neurotransmitters which cooperate between themselves maintaining the proper functioning of the brain. GABA neurons carry inhibitory signals that help keep brain activity at optimal levels of operation, Glutamate, on the other hand, carry excitatory signals. As the interplay between these two exists they keep the dopamine levels in the average levels. The disruption of GABA-ergic transmission in schizophrenia may induce alternations in dopaminergic neurotransmission providing no inhibitory effect to the central glutamate activity, resulting in the rise of the dopamine levels being associated with psychosis precipitation. Benzodiazepines are believed to reduce presynaptic dopamine release at the mesolimbic level and delay postsynaptic adaptation of dopaminergic neurons to antipsychotics potentiating the action of antipsychotics in resistant schizophrenia. Benzodiazepines also act on mesocortical regions where antipsychotics are less effective and where there is a particular sensitivity to stress. This association is particularly useful in resistant patients or in patients with severe anxiety with or without intolerance to antipsychotics. Improvement concerns anxious symptoms but also positive symptoms (hallucinations, delirium and dissociative syndrome) and negative (social withdrawal, affect flattening). As the available studies are limited there is some clinical evidence that the use of antipsychotic drugs with addition of benzodiazepines can provide better general outcome in ill patients than antipsychotics administration alone

OVERLAPPING PHENOMENA OF BIPOLAR DISORDER AND EPILEPSY - A COMMON PHARMACOLOGICAL PATHWAY

Background: Studies and data on prevalence, recognition and clinical features of bipolar disorder (BD) in epilepsy remain limited. Still, there is a growing evidence of BD and epilepsy being frequent co-morbid conditions with some features suggesting shared pathophysiological mechanisms that include the episodic course of both conditions, the possible kindling mechanism and the efficacy of some antiepileptic drugs (AEDs) in BD. Subjects and methods: The aim of this paper is to review concepts of overlapping phenomena of bipolar disorder and epilepsy. A literature review of the theoretical bases of the relationship between BD and epilepsy is presented. Conclusions: The comorbidity of epilepsy and mood disorders was a subject of interest of many studies for decades. Bipolar disorder and epilepsy have a number of clinical, biochemical and pathophysiological features in common. Bipolar disorder in epilepsy, excluding the ictal or periictal symptoms, can be categorized using standardized measures. Standardized psychiatric interview procedures based on DSM criteria like SCID-I or MINI provide comprehensive way to diagnose mood disorders in patients with epilepsy

BENZODIAZEPINES AS ADJUNCTIVE THERAPY IN TREATMENT REFRACTORY SYMPTOMS OF SCHIZOPHRENIA

Antipsychotics are a key intervention strategy in pharmacotherapy in schizophrenia. However, the benzodiazepines are often prescribed to control sleep disturbances, anxiety or hostile behaviour. There is some evidence supporting the combination therapy with antipsychotics and benzodiazepines providing beneficiary treatment effect to the psychosis in positive and negative symptom domains as well as catatonia or adverse reactions to antipsychotic drugs. In particular, in a population suffering from residual symptoms of schizophrenia, in particular anxiety, emotional flattening, being refractory to approved treatment strategies, benzodiazepines as add-on to antipsychotics seem to be an option. There is rationale for the therapeutic use for long-acting benzodiazepines as the treatment of option with limited literature indicating the use of chlordiazepoxide, and diazepam. The paper reviews the best clinical practice indications for benzodiazepines as the add-on treatment to antipsychotics in schizophrenia

IMPULSIVITY IN ANXIETY DISORDERS. A CRITICAL REVIEW

Background: Anxiety symptoms and disorders are common. High comorbidity between anxiety and other psychiatric disorders has been observed in community. Still, the relationship between impulsivity and anxiety disorders is controversial and not well explored. Material and methods: The aim of this paper is to review measures of trait impulsivity in anxiety disorders. A literature review of the theoretical bases of the relationship between anxiety disorders and impulsivity is presented. Results: Impulsivity is a key feature of numerous psychiatric disorders. Traditional conceptualizations suggest that impulsivity might display a negative relationship with anxiety. However, an association of impulsivity in patients with anxiety disorders is present. Some studies support proposition that anxiety may influence impulsivity in individuals with predisposition toward behavioural disinhibition. Conclusion: There is a link between anxiety and impulsivity in psychiatric patients characterized by problems with impulse control (e.g. pathological gambling, self-harming behaviour, eating disorders), mood disorders and anxiety disorders. Behavioural and pharmacological interventions for decreasing impulsivity may effectively be used in the treatment

CORTISOL AS AN INDICATOR OF HYPOTHALMIC-PITITUARY-ADRENAL AXIS DYSREGULATION IN PATIENTS WITH PANIC DISORDER: A LITERATURE REVIEW

Dysregulation of hypothalamic–pituitary-adrenal axis (HPA) is seen in numerous mental disorders. Data of HPA axis disturbance in panic disorder are inconsistent. In panic disorder HPA axis hyperactivity has been observed with elevated cortisol levels. However, hypocortisolism has also been noted. Salivary cortisol as a biomarker of HPA-axis activity has received special attention. The aim of this paper is to review the findings on cortisol levels in panic disorder

IMPULSIVITY AND PANIC DISORDER: AN EXPLORATORY STUDY OF PSYCHOMETRIC CORRELATES

Background: Impulsivity is associated with a wide variety of psychiatric disorders. However, the relationship between anxiety and impulsivity is not well explored. The objective of this study was to examine whether anxiety symptoms correlate with impulsivity in patients with panic disorder. Subjects and methods: We examined 21 psychotropic drug-naïve patients with panic disorder recruited from the outpatient setting. The severity of Panic Disorder was assessed with Panic and Agoraphobia Scale (PAS)-clinical rating version. Impulsivity was evaluated with Barratt Impulsiveness Scale, 11th version (BIS-11). Results: Our findings indicate the correlation between specific dimensions of impulsivity and selected subscales of Panic and Agoraphobia Scale. The positive correlation between attentional and non-planning dimensions of impulsivity, ‘disability’ and ‘worries about health’ in drug-naïve patients with PD was observed. Conclusions: The findings corroborate with the prior reports of higher impulsivity trait among patients with anxiety disorders