Serotonin syndrome in elderly patients treated for psychotic depression with atypical antipsychotics and antidepressants: two case reports

We report two cases of serotonin syndrome in elderly patients during treatment of psychotic depression with atypical antipsychotics and antidepressants. The first case is a 69-year-old man who was admitted for depression with psychosis and treated with trazodone, risperidone, and sertraline. Subsequently, he developed myoclonus, tremor, cogwheel rigidity, and diaphoresis. The second case is a 72-year-old female initially admitted to a medical inpatient unit for a change in mental status that presented as increased confusion, lethargy, slurred speech, and a fever of 101.5 degrees. She had been on phenelzine and quetiapine. In both cases, all symptoms resolved within 24 hours of the psychotropics being stopped. In both cases, we believe that serotonin syndrome was produced by a combination of an antidepressant and an atypical antipsychotic. There have been several case reports of serotonin syndrome from similar combinations of antidepressant and atypical antipsychotic treatment. Clinicians treating elderly patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome.     

Social anxiety and premorbid personality disorders in paranoid schizophrenic patients treated with clozapine

The concept of anxiety as a distinct comorbid disorder in schizophrenia has recently been rediscovered after having been neglected for a long period of time due to both theoretical and clinical approaches adopted from the appearance of the first edition of the Diagnostic and Statistical Manual of Mental Disorders in 1950. This rediscovery was accentuated by the fact that the concept of comorbidity in various psychiatric disorders has recently won widespread favor within the scientific community, and that the use of atypical neuroleptic medication to treat patients with schizophrenia has been reported to lead to the emergence of anxiety symptoms. Of the atypical neuroleptic medications used to treat schizophrenia, clozapine has most frequently been reported to induce anxiety symptoms. In this paper, 12 cases of patients with paranoid schizophrenia who developed social phobia during clozapine treatment are reported, and their response to fluoxetine augmentation is assessed. Premorbid personality disorders were also investigated; patients were assessed using the Structured Clinical Interview for DSM-III-R-Patient Version and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). In addition, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Liebowitz Social Anxiety Scale (LSAS), the Frankfurt Beschwerde Fragebogen (Frankfurt Questionnaire of Complaints), and the Brief Psychiatric Rating Scale were used to rate clinical symptomatology. All patients were reevaluated after 12 weeks of cotreatment with clozapine and fluoxetine. In 8 (66.6%) of the 12 cases, symptoms responded (>/=35% LSAS score reduction) to an adjunctive regimen of fluoxetine. Furthermore, in 7 (58.3%) of the 12 cases, an anxious personality disorder (avoidant=33.3%; dependent=25%) was identified, but no significant differences in the prevalence of comorbid personality disorders emerged in comparison with a group of 16 patients with paranoid schizophrenia treated with clozapine who did not show symptoms of social phobia. The clinical relevance of the assessment and treatment of anxiety disorders is discussed in light of a clinical therapeutic approach that overcomes the implicit hierarchy of classification. Considering that the onset of anxiety-spectrum disorders (such as social phobia) can occur during the remission of psychotic symptoms in clozapine-treated patients with schizophrenia, a comprehensive approach to pharmacological therapy for patients with schizophrenia (or, at least for those treated with clozapine) should be adopted.     

The paradox of quetiapine in obsessive-compulsive disorder

Schizophrenia and obsessive-compulsive disorder (OCD) have historical, clinical, and epidemiological links. The clinical use of atypical neuroleptics (ie, dual serotonin-dopamine antagonists) to treat both conditions sheds a new light on them. We report the first two cases of obsessive-compulsive symptoms (OCS) induced by quetiapine in schizophrenia patients. A case of successful augmentation by quetiapine in refractory OCD is also presented. A review of the literature on OCS induced by atypical neuroleptics follows. This paradoxically induced OCD symptomology in schizophrenia patients administered atypical neuroleptics is discussed from new pathophysiological and clinical perspectives. The discussion emphasizes the prognostic implications of OCS in schizophrenia and available therapies for this comorbidity.     

The illness concept in adolescent psychiatry

This paper introduces some important views on the clinical entities of the adolescent psychiatry in Japan. Shimizu shows the transitional region between neurosis, schizophrenia and normal. Murakami's new classification tells the relationship among the psychiatric disorders, especially about the borderline disorder. Hatotani's scheme deals with the atypical psychoses very well. According to the idea of Griesinger's "Einheitspsychose" arranges my symptomatic picture several ambiguous symptoms of the adolescent psychiatric disorders. In this picture we can understand the meaning of the borderline disorder. At last I give the catastrophic model of psychiatric disorders.     

The effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage

Clozapine is an atypical antipsychotic drug that has been shown to improve spatial memory in some animal models; however its efficacy in reversing spatial memory impairment in rats with hippocampal lesions is unknown. To address this issue, we tested the effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage in three separate experiments. In each experiment, adult male rats received sham surgery or direct stereotaxic infusions of the excitotoxin, NMDA, into the hippocampus. In the first study, seven days after surgery, the sham control animals received daily saline injections while the lesioned animals were split into two groups that received daily saline or clozapine (2.0 mg/kg, sc) injections. During the fifth week of injections, all animals were tested in a food-motivated delayed spatial alternation task. Saline-treated rats with excitotoxic hippocampal damage displayed significant deficits in delayed spatial alternation. Daily clozapine injections completely reversed this deficit. In a second experiment, it was found that clozapine treatment limited to the testing days only did not improve alternation performance in lesioned rats. Finally, in a third experiment, chronic clozapine treatment did not improve alternation performance in lesioned rats that were pre-trained in the alternation task prior to surgery. These results suggest that chronic, but not acute, clozapine treatment enables rats with hippocampal damage to develop new spatial learning, but can not rescue old spatial learning established prior to damage. These results may have implications for the treatment of cognitive deficits caused by hippocampal dysfunction in disorders such as schizophrenia, Alzheimer's disease, and others.     

Differential diagnosis of endogenous psychoses in relation to a symptom catalog

The paper introduces a catalog of symptoms to promote in the field of endogenous psychoses differentiated diagnosis, at the same time constituting a prognosis. Symptoms should be more minutely differentiated than is customary in psychiatric questionnaires. Manic-depressive disorders and purely phasal psychoses are distinguished solely in the clinical evaluation. Thus benign cycloid psychoses can be distinguished from malignant unsystematic schizophrenia.     

Pharmacological treatment effects on eye movement control

The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second- generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson’s disease, and Huntington’s disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.     

Pharmacological treatment effects on eye movement control

The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second- generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson’s disease, and Huntington’s disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.     

Augmentation strategies in the treatment of schizophrenia

Use of augmenting agents in schizophrenia is a common practice in response to resistant symptoms or comorbid illness. Increasingly, clinicians are combining more than one antipsychotic agent, despite a lack of evidence from controlled studies to support this approach. A rationale can be made for adding higher-potency agents to clozapine in an attempt to optimize D2 dopamine receptor blockade, but this strategy requires further study before it should be adopted in clinical practice. Older reports have explored the use of antidepressants, mood stabilizers, and anxiolytics as augmenting agents. These agents appear to improve comorbid affective or anxiety symptoms, but earlier evidence of improvement in psychotic or negative symptoms has not been replicated consistently. Glutamatergic agents acting at the glycine coagonist site of the N-methyl-d-aspartate receptor, including glycine, d-cycloserine, and d-serine, have demonstrated impressive therapeutic effects for negative symptoms when added to conventional neuroleptic agents, but do not appear to enhance clozapine efficacy. Given the high rates of symptom persistence and disability associated with schizophrenia, the need for augmentation strategies is great, but no approach has clearly emerged as effective for a substantial portion of patients. Although certain approaches may prove helpful for individual patients, augmentation should not be used unless monotherapy has been optimized, and should not be continued long-term unless benefits are clear.     

Psychotic manifestations in a patient with mental retardation and a 6.2 megabase deletion at the distal short arm of chromosome 12

Genetic factors are known to contribute to the development of schizophrenia and related psychoses. Cytogenetic abnormalities have been occasionally found in patients with psychotic disorders and, thus, have helped identify candidate gene contributors for these conditions. The individual described here first presented with mental retardation and anxiety disorder in his mid-childhood. In his early 20s, the patient started exhibiting various psychotic manifestations, including delusions and hallucinations. His psychotic symptoms were difficult to control with psychotropic medications. The family history was negative for psychiatric disorders. This patient was found to have a 6.2 megabase deletion of the terminal portion of the short arm of chromosome 12 that was characterized using fluorescence in situ hybridization and microarray comparative genomic hybridization analysis. The maternal chromosomes were normal, but the paternal chromosomes could not be tested. To-date such a chromosomal abnormality has not been described in association with schizophrenia/psychosis. This case suggests that psychosis-associated gene(s) may be located in the terminal region of the short arm of chromosome 12.     

The clinical overlap between the corticobasal degeneration syndrome and other diseases of the frontotemporal spectrum: three case reports

The corticobasal degeneration syndrome has been suggested to be part of a complex of conditions (including the different subtypes of frontotemporal dementia and progressive supranuclear palsy), which reflect a spectrum of pathological substrates. This concept is supported by the frequent clinical overlap that can be observed among patients diagnosed with these conditions. We report three clinical cases, characterized by the overlap of the clinical features of corticobasal degeneration syndrome with, respectively, nonfluent progressive aphasia, progressive supranuclear palsy and semantic dementia. Current diagnostic criteria emphasize differences in clinical presentation, which probably reflect the preferential location of pathology in the early stages of disease. However, with disease progression, a considerable clinical overlap can be expected among the different syndromes. This concept should be extended not only to the cognitive and behavioural features of the frontotemporal dementia subtypes, but also to the movement disorders of corticobasal degeneration and supranuclear palsy.     

Trichotillomania in a schizophrenia patient

Comorbidity of trichotillomania with different psychiatric disorders is common. However, until recently there have been no reports of trichotillomania in schizophrenia patients. In this article, the case of a female schizophrenia patient with trichotillomania is reported. Her schizophrenia was being treated with risperidone. Citalopram was later administered as an augmentation to risperidone. This combination therapy presented a partial response of trichotillomania without exacerbating schizophrenia symptoms.     

Does symptomatic schizophrenia exist?

The question if there are "symptomatic schizophrenias" has been discussed since the 20s. Schizophrenic psychoses caused be definable and well known brain diseases are presented. All schizophrenic symptoms and syndromes, the first rank symptoms (K. Schneider) too, occur in somatically founded psychoses. The group of paroxysmal transition syndromes in the sense of aura prolongata (continua) and the episodic schizophrenic psychoses in psychomotor epilepsy may be a model for the schizophrenia research. Vital threatening, so-called pernicious catatonic schizophrenias are found on the basis of infectious brain diseases, sometimes only diagnosed in autopsy. Beside acute and reversible symptomatic schizophrenic psychoses there are, even if rarely, recurrent and chronic courses of symptomatic schizophrenias. That certain conditions for the developing of symptomatic schizophrenias are rarely realised, could be an explanation for their rarity. Some findings indicate that the limbic system is significant for symptomatic (and idiopathic) schizophrenic psychoses and the pre- and postpsychotic basic stages determined by dynamic and cognitive basic symptoms, which are phenomenologically very similar to aura symptoms released by stereoelectroencephalographic depth recordings (Wieser). The characteristic features of marked fluctuation, discontinuity and insteadiness of the cognitive thought, perception, psychomotor and cenesthetic phenomena do not speak against an organic brain disorder provided that the traditional process hypothesis is abandoned in favor of a neurobiochemic disorder, fluctuating on its part depending on endogenous as well as psychic-reactive factors.     

Provoking endogenous psychoses

For six forms of endogenous psychosis, causal agencies were sought to establish endogenous, physical, and mental provocation. Endocrine causes were found most frequently, 17.5%, in mixed bipolar disorders, followed by cycloid psychoses, 8.5%, which in this respect appear to be closer to the mixed bipolar psychoses, than the unipolar forms at 4.4%. Among the physical causes, the difference in affective psychoses is not particularly great. Cycloid psychoses head the list at 9%. Among the mental causes, pure phase psychoses account for the greatest number, 12.7%, by a wide margin. The three unsystematic forms of schizophrenia revealed a slender link with their causes. Clear distinctions among the causes of the six forms were thus demonstrated.     

Pharmacotherapeutic options in the treatment of comorbid depression and anxiety

Although anxiety and mood disorders are listed as separate disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, they frequently coexist. They may be expressed phenotypically as comorbidities or as the provisional entity mixed anxiety-depressive disorder. Patients with both anxiety and depression are more symptomatic, use more health care resources, and have a worse prognosis than those with a single disorder. Recognizing and treating these patients are challenges for physicians because the symptoms of the two disorders often overlap. Administration of effective treatment, comprising both anxiolytic and antidepressant effects, can reduce patient distress and disability, as well as inappropriate utilization of medical services. Medications such as tricyclic antidepressants, selective serotonin reuptake inhibitors, nefazodone, venlafaxine XR (extended release) and mirtazapine, are highly effective in treating comorbid depression and anxiety. These newer agents now represent the pharmacotherapeutic treatments of choice for the comorbid conditions.     

Psychotische Störungen und komorbide Suchterkrankungen

Approximately half of the people with psychotic disorders from the schizophrenia group also develop a comorbid addictive disorder during their lifetime. These so-called dual diagnosis patients (DD) are difficult to treat. They have poor compliance and frequent relapses, they often present with aggressive behavior towards themselves and others and the long-term sociorehabilitative outcomes are poor.In this article the different models for the understanding of the high comorbidity between psychoses and substance use disorders are explained and the principles for an integrated treatment of DD patients are outlined. Low-threshold, motivational, integrated treatment programs with psychoeducative and behavioral therapeutic elements are helpful and should be more extensively implemented; however, long-term treatment methods are needed and therapeutic goals must be realistic and not set too high.     

Infectious and immune factors in the pathogenesis of neurodevelopmental disorders: epidemiology, hypotheses, and animal models

Both genetic and environmental factors contribute to the pathogenesis of a wide variety of neurodevelopmental disorders, including autism, mental retardation, and schizophrenia. Some heritable disorders approach 100% penetrance; nonetheless, even in these disorders, subtle aspects of clinical disease expression may be influenced by the environment. In other disorders with genetic influences, exogenous factors, and the timepoint(s) during nervous system development at which they are introduced, modulate expression of disease. Elucidation of the mechanisms guiding this intricate interplay between host response genes, environmental agents, and the neurodevelopmental context within which these interactions occur, is necessary to understand the continuum of clinical outcomes. This chapter will review the evidence that infectious and immune factors may contribute to the pathogenesis of neurodevelopmental disorders, describe an animal model of neurodevelopmental disorders based upon viral infection, identify processes by which neural circuitry may be compromised, and outline areas for future research.     

Treatment of Diogenes Syndrome with Risperidone

Diogenes syndrome is characterized by shameless neglect of the body and personal environment, hoarding, and the rejection of any help. It occurs among patients with and without other psychiatric disorders. The initial treatment should be a behavioral program, but there is no information about the pharmacological treatment of this syndrome. We report the case of a 77-year-old woman with symptoms of Diogenes syndrome. After an unsuccessful behavioral program, treatment with risperidone initially improved the behavioral symptoms but impaired cognitive function, and was followed by marked global deterioration, fulfilling criteria for dementia.