Patricia I. Rosebush

Catatonia and Its Treatment

Psychiatric diagnoses are currently categorized on a syndromic basis. The syndrome of catatonia, however, remains in a diagnostic limbo, acknowledged predominantly as a subtype of schizophrenia. Yet, catatonia is present in about 10% of acutely ill psychiatry patients, only a minority of whom have schizophrenia. Among those with comorbid affective disorders, who comprise the largest subgroup of catatonic patients, the catatonic signs typically resolve dramatically and completely with benzodiazepine therapy. Those with schizophrenia respond less reliably, suggesting that the underlying processes causing the catatonia may be different in this group. The majority of patients with catatonia have concurrent psychosis. Failure to treat the catatonia before institution of antipsychotic medication may increase the risk of inducing neuroleptic malignant syndrome. At this point of time, the pathobiology of catatonia is unknown; the major reason for considering catatonia as a separate diagnostic entity would be to increase recognition of this eminently treatable neuropsychiatric syndrome.

Neurologic side effects in neuroleptic-naïve patients treated with haloperidol or risperidone

Objective: To compare the side effect profile of risperidone with that of oral haloperidol in patients with no previous exposure to antipsychotic drugs (APDs). Background: Early studies suggested that the APD risperidone may have a side effect profile comparable with that of placebo. These early studies involved patients with chronic schizophrenia and a long history of APD use. Very little information is available regarding the neurologic side effects of risperidone in patients without previous APD exposure. Methods: The authors prospectively studied 350 consecutive neuroleptic-naive patients admitted to their acute-care psychiatry service; 34 of these were treated with risperidone (mean dose, 3.2 mg/d) and 212 were treated with low-dose haloperidol (mean dose 3.7 mg/d). All patients were assessed on admission and twice weekly thereafter using rating scales for dystonia, parkinsonism, akathisia, and dyskinesia. Results: The incidence and severity of dystonic reactions, akathisia, parkinsonism, and dyskinesia were comparable in the risperidone- and haloperidol-treated groups. Conclusions: The neurologic side effect profile of low-dose risperidone is comparable with that of haloperidol in patients receiving APDs for the first time. Risperidone may not be a useful alternative to typical APDs for patients with PD and psychosis.

An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method.

OBJECTIVE The lack of generally accepted diagnostic criteria for neuroleptic malignant syndrome (NMS) impedes research and clinical management of patients receiving antipsychotic medications. The purpose of this study was to develop NMS diagnostic criteria reflecting a broad consensus among clinical knowledge experts, represented by an international multispecialty physician panel. PARTICIPANTS Eleven psychiatrists, 2 neurologists, 2 anesthesiologists, and 2 emergency medicine specialists participated in a formal Delphi consensus procedure. EVIDENCE A core bibliography consisting of 12 prominent, current reviews of the NMS literature was identified by an objective, comprehensive electronic search strategy. Each panel member was given a copy of these references and asked to examine them before commencing the survey process. CONSENSUS PROCESS After reviewing the core bibliography, panel members were asked to list any clinical signs or symptoms or diagnostic studies that they believed, on the basis of their knowledge and clinical experience, were useful in making a diagnosis of NMS. In subsequent survey rounds, panel members assigned priority points to these items, and items that failed to receive a minimum priority score were eliminated from the next round. Information about individual panel member responses was fed back to the group anonymously in the form of the group median or mean and the number of members who had ranked or scored each survey item. The a priori consensus endpoint was defined operationally as a change of 10% or less in the mean priority score for any individual item, and an average absolute value change of 5% or less across all items, between consecutive rounds. The survey was conducted from January 2009 through September 2009. RESULTS Consensus was reached on the fifth round regarding the following criteria: recent dopamine antagonist exposure, or dopamine agonist withdrawal; hyperthermia; rigidity; mental status alteration; creatine kinase elevation; sympathetic nervous system lability; tachycardia plus tachypnea; and a negative work-up for other causes. The panel also reached a consensus on the relative importance of these criteria and on the following critical values for quantitative criteria: hyperthermia, > 100.4°F or > 38.0°C on at least 2 occasions; creatine kinase elevation, at least 4 times the upper limit of normal; blood pressure elevation, ≥ 25% above baseline; blood pressure fluctuation, ≥ 20 mm Hg (diastolic) or ≥ 25 mm Hg (systolic) change within 24 hours; tachycardia, ≥ 25% above baseline; and tachypnea, ≥ 50% above baseline. CONCLUSIONS These diagnostic criteria significantly advance the field because they represent the consensus of an international multispecialty expert panel, include critical values, provide guidance regarding the relative importance of individual elements, and are less influenced by particular theoretical biases than most previously published criteria. They require validation before being applied in clinical settings.

The Psychiatric Manifestations of Mitochondrial Disorders: A Case and Review of the Literature

OBJECTIVE Mitochondrial disorders are caused by gene mutations in mitochondrial or nuclear DNA and affect energy-dependent organs such as the brain. Patients with psychiatric illness, particularly those with medical comorbidities, may have primary mitochondrial disorders. To date, this issue has received little attention in the literature, and mitochondrial disorders are likely underdiagnosed in psychiatric patients. DATA SOURCES This article describes a patient who presented with borderline personality disorder and treatment-resistant depression and was ultimately diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3271. We also searched the literature for all case reports of patients with mitochondrial disorders who initially present with prominent psychiatric symptoms by using MEDLINE (from 1948-February 2011), Embase (from 1980-February 2011), PsycINFO (from 1806-February 2011), and the search terms mitochondrial disorder, mitochondria, psychiatry, mental disorders, major depression, anxiety, schizophrenia, and psychosis. STUDY SELECTION Fifty cases of mitochondrial disorders with prominent psychiatric symptomatology were identified. DATA EXTRACTION Information about the psychiatric presentation of the cases was extracted. This information was combined with our case, the most common psychiatric manifestations of mitochondrial disorders were identified, and the important diagnostic and treatment implications for patients with psychiatric illness were reviewed. RESULTS The most common psychiatric presentations in the cases of mitochondrial disorders included mood disorder, cognitive deterioration, psychosis, and anxiety. The most common diagnosis (52% of cases) was a MELAS mutation. Other genetic mitochondrial diagnoses included polymerase gamma mutations, Kearns-Sayre syndrome, mitochondrial DNA deletions, point mutations, twinkle mutations, and novel mutations. CONCLUSIONS Patients with mitochondrial disorders can present with primary psychiatric symptomatology, including mood disorder, cognitive impairment, psychosis, and anxiety. Psychiatrists need to be aware of the clinical features that are indicative of a mitochondrial disorder, investigate patients with suggestive presentations, and be knowledgeable about the treatment implications of the diagnosis.

Catatonia After Benzodiazepine Withdrawal

The use of benzodiazepine medication is associated with a variety of acute and well-recognized withdrawal syndromes including anxiety, agitation, insomnia, and confusion. Catatonia has not previously been described. We report five patients who became catatonic after withdrawal of benzodiazepines. All five were older individuals (53-88 years) who had acutely become immobile, mute, and rigid with refusal or inability to eat or drink. Each of the five showed pronounced and rapid improvement after administration of low-dose lorazepam, which has previously been reported to be effective in the treatment of catatonia. Careful review of the records showed that each of the patients had been taking benzodiazepine medication for anywhere from 6 months to 15 years and that it had been rapidly tapered or abruptly discontinued 2 to 7 days before the onset of catatonia. These cases illustrate that severe and potentially life-threatening catatonia can develop in the wake of benzodiazepine withdrawal. Older individuals may be particularly vulnerable to this side effect.

The mitochondrial genome and psychiatric illness

Psychiatric disorders are a leading cause of morbidity and mortality, yet their underlying pathophysiology remains unclear. Searches for a genetic cause of bipolar disorder, schizophrenia, and major depressive disorder have yielded inconclusive results. There is increasing interest in the possibility that defects in the mitochondrial genome may play an important role in psychiatric illness. We undertook a review of the literature investigating mitochondria and adult psychiatric disorders. MEDLINE, PsycINFO, and EMBASE were searched from their inception through September 2011, and the reference lists of identified articles were reviewed for additional studies. While multiple lines of evidence, including clinical, genetic, ultrastructural, and biochemical studies, support the involvement of mitochondria in the pathophysiology of psychiatric illness, many studies have methodological limitations and their findings have not been replicated. Clinical studies suggest that psychiatric features can be prominent, and the presenting features of mitochondrial disorders. There is limited but inconsistent evidence for the involvement of mitochondrial DNA haplogroups and mitochondria‐related nuclear gene polymorphisms, and for mitochondrial ultrastructural and biochemical abnormalities in psychiatric illness. The current literature suggests that mitochondrial dysfunction and mitochondrial genetic variations may play an important role in psychiatric disorders, but additional methodologically rigorous and adequately powered studies are needed before definitive conclusions can be drawn.

The Psychiatric Presentation of Mitochondrial Disorders in Adults

Although comorbid psychiatric illness is increasingly being recognized in patients with mitochondrial disorders, there has been relatively little attention to psychiatric symptomatology as the primary clinical presentation. The authors report detailed clinical, biochemical, neuroradiological, and genetic findings in a series of 12 patients with mitochondrial disorders in whom psychiatric symptoms were a prominent aspect of the clinical presentation. The psychiatric presentations included depression, anorexia nervosa, bipolar disorder, and obsessive-compulsive disorder. A review of the literature, in conjunction with the present series, indicates that psychiatric symptoms can be the presenting feature of mitochondrial disorders and highlights the importance of considering this diagnosis.

Neuroleptic malignant syndrome: a neuroimmunologic hypothesis

Neuroleptic malignant syndrome is a fulminant and life-threatening toxidrome that occurs in an estimated 0.07% to 3.23% of patients treated with antipsychotic medication.[1][1],[2][2] Patients typically present with fever, rigidity, changes in mental status and autonomic instability, often after the

Catatonia: Our current understanding of its diagnosis, treatment and pathophysiology

Catatonia is a psychomotor syndrome that has been reported to occur in more than 10% of patients with acute psychiatric illnesses. Two subtypes of the syndrome have been identified. Catatonia of the retarded type is characterized by immobility, mutism, staring, rigidity, and a host of other clinical signs. Excited catatonia is a less common presentation in which patients develop prolonged periods of psychomotor agitation. Once thought to be a subtype of schizophrenia, catatonia is now recognized to occur with a broad spectrum of medical and psychiatric illnesses, particularly affective disorders. In many cases, the catatonia must be treated before any underlying conditions can be accurately diagnosed. Most patients with the syndrome respond rapidly to low-dose benzodiazepines, but electroconvulsive therapy is occasionally required. Patients with longstanding catatonia or a diagnosis of schizophrenia may be less likely to respond. The pathobiology of catatonia is poorly understood, although abnormalities in gamma-aminobutyric acid and glutamate signaling have been suggested as causative factors. Because catatonia is common, highly treatable, and associated with significant morbidity and mortality if left untreated, physicians should maintain a high level of suspicion for this complex clinical syndrome. Since 1989, we have systematically assessed patients presenting to our psychiatry service with signs of retarded catatonia. In this paper, we present a review of the current literature on catatonia along with findings from the 220 cases we have assessed and treated.

Persistent loss of tyrosine hydroxylase immunoreactivity in the substantia nigra after neuroleptic withdrawal

A 37 year woman developed neuroleptic induced parkinsonism that persisted long after the drug had been discontinued. This prompted a study of the effect of an eight week course of haloperidol (HAL) followed by two week withdrawal, on dopaminergic neurons of the substantia nigra in rats. Animals treated with HAL showed a highly significant 32%-46% loss of tyrosine hydroxylase (TH) immunoreactive neurons in the substantia nigra, and 20% contraction of the TH stained dendritic arbour. Neuroleptic drug induced downregulation of nigral dopaminergic neurons may help to explain the persistent parkinsonism found in many patients after withdrawal of medication.