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Clinical Trial, Phase I 2005; 26(6): 685-689 PubMed PMID: 16380684 Citation  Keywords:  Adult, Antipsychotic Agents:therapeutic use, Benzodiazepines:therapeutic use, Brain Mapping, Cerebrovascular Circulation:drug effects, Cysteine:analogs & derivatives, Frontal Lobe:blood supply, Humans, Male, Middle Aged, Organotechnetium Compounds, Psychi.   

OBJECTIVES: Altered regional cerebral blood flow (r-CBF) is mentioned as one of possible etiological factors or as a consequence of schizophrenia. Perfusion scintigraphic brain studies with SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) can detect areas of the brain with altered perfusion during the disease. Conflicting data exist on follow-up after treatment. The aim of our study was to evaluate r-CBF in acute first-episode schizophrenia and early effect of antipsychotic drugs on r-CBF.

DESIGN AND SETTING: Clinical criteria for schizophrenia were met according to International Classification of Diseases-10th Edition (ICD-10). Psychic status and severity of the disease in each patient were evaluated with psychiatric interview, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) on the same day as the scintigraphic study. Brain perfusion SPECT was performed 20 minutes after 99mTc-ECD application. R-CBF was measured in 9 first-episode schizophrenic male patients 2-7 (median 6) days after the beginning of antipsychotic treatment and 8-15 (median 9) weeks later. Semiquantitative analysis of r-CBF was performed with cerebellum as the reference region. R-CBF was evaluated for 12 regions in each study.

RESULTS: Decrease in perfusion in comparison to cerebellum was detected in left (90%) and right (93%) frontal lobes. Increase in perfusion between the first (t1) and the second (t2) investigation was significant (p<0.05) for both frontal regions (left 94%, right 97%). Significant decrease in PANSS (p<0.05) and CGI (p<0.001) scores was noted and correlated well with the increase of r-CBF.

CONCLUSIONS: Our findings implicate that patients with first-episode schizophrenia have significant left hypoperfusion relative to the right in dorsolateral frontal lobes. Increased blood flow was observed bilaterally in dorsolateral frontal lobes after 10 weeks of antipsychotic medication. Significant amelioration of r-CBF correlated with clinical improvement....

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Journal Article 2005; 26(Suppl 1): 67-73 PubMed PMID: 16361989 Citation  Keywords:  Antidepressive Agents, Second-Generation:therapeutic use, Antipsychotic Agents:therapeutic use, Bipolar Disorder:diagnosis, Cyclothymic Disorder:drug therapy, Humans, Treatment Outcome,.   

: Rapid cycling (RC) bipolar disorder is defined as four or more affective episodes within one year. RC bipolar disorder constitutes one of the most difficult forms of the illness to treat effectively. According to several studies, RC bipolar patients have more severe symptoms than non-rapid cycling bipolar patients. Most studies indicate that only 10% to 20% of patients with bipolar disorders experience rapid cycling, but this is of great concern to psychiatrists because of its association with treatment refractoriness. Second generation antipsychotics are increasingly being used in the treatment of bipolar disorder. A first step in the management of rapid-cycling bipolar disorder is the thorough assessment of possible medications or environmental factors that may destabilize the disorder and contribute to the recurrence of episodes, increasing cycle frequency, or both. All currently approved antidepressant drugs pose some risk of mood destabilization, but the risk is highest for tricyclic antidepressants. Discontinuation of antidepressants should be the first step in the management of RC patients....

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Journal Article 2005; 26(Suppl 1): 27-47 PubMed PMID: 16361987 Citation  Keywords:  Antidepressive Agents, Second-Generation:therapeutic use, Antipsychotic Agents:therapeutic use, Bipolar Disorder:drug therapy, Clinical Trials as Topic, Depressive Disorder:diet therapy, Humans, Treatment Outcome,.   

: Antidepressants have insufficient effect in 20-40% of patients treated for depressive disorders. This is particularly true for psychotic and agitated depression. When administered on a long-term basis, antidepressants cause a switch into mania in 25-40% of patients and induce rapid cycling. Classical antipsychotics have exhibited good therapeutic efficacy in the treatment of various forms of depression, especially psychotic and agitated forms, albeit burdened with many, above all extrapyramidal, side effects. When administered over long periods of time, classical antipsychotics may have a depressogenic effect. Second-generation antipsychotics have started to be increasingly used in this indication for a variety of reasons including: their antidepressant effect attributable to raised concentrations of catecholamines in the prefrontal cortex, their impact on serotonin transmission, their antipsychotic effect due to their mode of action including the mesolimbic blockade of dopamine D2 receptors, and the low incidence of extrapyramidal and other side effects. The following text encompasses the results of controlled trials using second-generation antipsychotics in the treatment of acute depressive disorders....

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Journal Article 2005; 26(Suppl 1): 9-25 PubMed PMID: 16361986 Citation  Keywords:  Acute Disease, Antidepressive Agents, Second-Generation:therapeutic use, Antimanic Agents:therapeutic use, Antipsychotic Agents:therapeutic use, Bipolar Disorder:drug therapy, Double-Blind Method, Drug Therapy, Combination, Humans, Randomized Controlled T.   

: The DSM-IV criteria for mania require: a distinct period that represents a break from pre-morbid functioning, a duration of at least one week, elevated or irritable mood, at least three to four classical manic signs and symptoms and the absence of any physical factors. Although not specifically mentioned in the ICD-10 or the DSM-IV definitions, delusional, hallucinatory, even first-rank, psychotic experiences can occur in mania. Acute mania can be subdivided into classical pure mania, mania with mood-congruent or mood-incongruent psychosis, mixed state and rapid-cycling mania. One quarter to two thirds of all manic episodes are associated with delusions, while 13% to 40% are associated with hallucinations. Mixed episode is a complex syndrome which is difficult to diagnose, has the most prolonged duration of bipolar episodes and more frequent psychotic profile than pure mania with high suicidality and poor response to drugs. Mixed state mania has been well known since Kreapelin and listed in classification systems with criteria that include both a manic and a major depressive episode nearly every day for at least a one-week period. On the other hand, mixed-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electro-convulsive therapy or light therapy) should not contribute toward a diagnosis of Bipolar I Disorder. Although, theoretically, mania is supposed to be resolved within 1-3 months even without treatment, psychiatric hospitalization is very common in especially severe cases due to functional impairment. Current treatments for mania aim to control the agitation, impulsivity, aggression and psychotic symptoms and to help patients regain their pre-morbid functionality. However, the clinical management of mania is challenging as most patients show syndromal remission but incomplete functional recovery after the first episode of mania....

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Journal Article 2005; 26(4): 327-335 PubMed PMID: 16136016 Citation  Keywords:  Acute Disease, Antipsychotic Agents:therapeutic use, Humans, Psychomotor Agitation:drug therapy, Psychotic Disorders:complications,.   

: Several psychotic disorders, including schizophrenia, may be associated with symptoms of acute agitation and aggression. While drug treatment of agitation is often essential, non-pharmacological interventions, both environmental and behavioral, also play important roles in the complex management of agitated patients. The most extensively used psychotropic drugs are parenteral formulas of conventional antipsychotics and benzodiazepines. Recently, injection forms of two second generation antipsychotics, olanzapine and ziprasidone, have become available. Both drugs have shown adequate efficacy and tolerability in several double-blind trials of intramuscular administration in acutely agitated psychotic patients. Compared to conventional medication, injection forms of the new antipsychotics may have a faster onset of action and more favorable profile of adverse events. Alternative approaches to injection administration include liquid drug formula, orally disintegrating tablets and wafers, treatment initiation with high doses, or rapid dose escalation. Evidence suggests that second-generation antipsychotics should be among the first-line choices in the treatment of agitation in acute psychosis....

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