Life-threatening Conditions in Psychiatry: Catatonia, Neuroleptic Malignant Syndrome, and Serotonin Syndrome

Definition

The catatonic syndrome comprises a constellation of motor and behavioral signs and symptoms that often occur in relation to neuromedical insults. Structural brain disease, intrinsic brain disorders (e.g., epilepsy, toxic-metabolic derangements, infectious diseases), systemic disorders that affect the brain, and idiopathic psychiatric disorders (such as affective and schizophrenic psychoses) have all been associated with catatonia. Catatonia was first named and defined in 1847 by Karl Kahlbaum, who published a monograph that described 21 patients with a severe psychiatric disorder.

Kahlbaum believed that patients with catatonia passed through several phases of illness: a short stage of immobility (with waxy flexibility and posturing), a second stage of stupor or melancholy, a third stage of mania (with pressured speech, hyperactivity, and hyperthymic behavior), and finally, after repeated cycles of stupor and excitement, a stage of dementia.

Kraepelin included catatonia in the group of deteriorating psychotic disorders named “dementia praecox.” Bleuler adopted Kraepelin's view that catatonia was subsumed under the heading of severe idiopathic deteriorating psychoses, which he renamed “the schizophrenias.” It is curious that while Kraepelin and Bleuler both seemed to understand that catatonic symptoms could emerge as part of a mood disorder or could result from neurologic, toxic-metabolic, and infectious etiologies, they persisted in categorizing it exclusively with the severe dilapidating psychoses.

As a result of their influence, catatonia was strongly linked with schizophrenia until the 1990s, and until fairly recently catatonia could only be diagnosed in the setting of schizophrenia. Thanks in large part to the work of Fink and Taylor, the Diagnostic and Statistical Manual of Mental Disorders, ed 4 (DSM-IV) was the first to include criteria for mood disorders with catatonic features and for catatonic disorder secondary to a general medical condition, as well as for the catatonic type of schizophrenia. In some measure due to lobbying from catatonia researchers, in DSM-5, catatonia is now subdivided into Catatonia Associated with Another Mental Disorder, Catatonic Disorder due to Another Medical Condition, and Unspecified Catatonia. The catatonic subtype of schizophrenia has been removed.

Under DSM-5, catatonia, whether a consequence of medical illness or a mental disorder, is diagnosed when the clinical picture includes at least three of the following 12 features: catalepsy, waxy flexibility, stupor, agitation, mutism, negativism (characterized by an apparently motiveless resistance to all instructions or by the maintenance of a rigid posture against attempts to be moved), posturing, mannerism, stereo­typy, grimacing, and echolalia or echopraxia.

Epidemiology and Risk Factors

Catatonia is a non-specific syndrome associated with a variety of etiologies. The rate of catatonia in the general psychiatric population varies according to the study design and diagnostic criteria. Prospective studies on patients hospitalized with acute psychotic episodes place the incidence of catatonia in the 7% to 17% range. In patients who suffer from mood disorders, rates have ranged from 13% to 31%. Catatonia appears commonly in those with bipolar disorder, with some suggesting that 20% of manic patients display at least one sign of catatonia. Some have contended that the incidence of catatonia has diminished in schizophrenia, but diagnostic and study design variations make this interpretation problematic. Patients with autism-spectrum disorders and developmental disorders appear to be at higher risk for developing catatonia. Personality disorders or conversion disorder have been cited as etiologic in a minority of catatonia cases.

Risk factors include: a history of catatonia; extrapyramidal symptoms (EPS); a mood disorder with psychomotor retar­dation or excitement (manic delirium); perinatal infec­tious disease; epilepsy or migraine; frontal, basal gangliar, brainstem, or cerebellar disease; dehydration; hyponatremia; weight loss; medications that lower seizure threshold, block dopamine, reduce GABA _A , or increase serotonin; long-term benzodiazepine or antiparkinsonian use with recent withdrawal or a decrease in dose; and low levels of serum iron.

Neuromedical “organic” etiologies account for 4% to 46% of cases in various series, underscoring the need for a thorough neuromedical work-up when catatonic signs are present. Though the current nosology does not allow for the diagnosis of catatonia in the setting of delirium, clinical experience suggests that delirium is often present in patients with catatonia. In a recent retrospective cohort analysis, encephalitis was the diagnosis most commonly associated with catatonia due to a medical condition. Absence of psychiatric history and a history of seizures predicted a primary medical, as opposed to primary psychiatric, etiology. Catatonia is idiopathic in 4% to 46% of cases in various case series.

Recently, attention has been drawn to cases of limbic encephalitis that are classically responsible for catatonic presentations. These can be secondary to paraneoplastic or immune causes. Acute or subacute onset (usually of less than 12 weeks), history of a tumor, infection, autoimmune disease along with lack of psychiatric history, and evidence of central nervous system (CNS) inflammation/infection (CSF pleocytosis, protein increase, positive culture; MRI and PET findings) are helpful in considering the many paraneoplastic, autoimmune, and infectious etiologies. Serum autoantibody titers are also available and can be helpful in determining etiology. Management is directed at the causative condition and includes surgical removal of an ovarian or testicular teratoma or other offending tumors and anti-inflammatory treatments (such as medications, intravenous IgG, and plasmaphoresis). However, use of lorazepam and electroconvulsive therapy (ECT) should not be neglected as potential treatments in cases with catatonia.

Subtypes

Several subtypes of catatonia have been described. Catatonic withdrawal, or stuporous catatonia, is characterized by psychomotor slowing, whereas catatonic excitement is characterized by hyperactivity. These presentations may alternate during the course of a catatonic episode. Catatonia that is associated with fever and autonomic instability is classified as lethal or malignant catatonia. Untreated malignant catatonia is now estimated to be fatal in 10%–20% of cases.

Kraepelin identified a “periodic” catatonia (with an onset in adolescence) characterized by intermittent excitement, followed by catatonic stupor and a remitting and relapsing course. In the 1930s this disorder was further described and distinguished by the rapid onset of a manic delirium, high temperatures, catatonic stupor, and a mortality rate in excess of 50%. Cases from the pre-neuroleptic era classically began with 8 days of intense, uninterrupted motor excitement; three out of four cases were fatal. In later cases, 60% of patients who received neuroleptics died. Afflicted patients were often bizarre and violent, refused to eat, and manifested intermittent mutism, posturing, catalepsy, and rigidity that alternated with excitement. When hyperactive, they were febrile, diaphoretic, and tachycardic. This stage would be followed by exhaustion, characterized by stupor and by high temperatures. Once stupor and rigidity emerged, patients were clinically indistinguishable from those with NMS. Periodic catatonia has been associated with various neuromedical and psychiatric etiologies.

The excited phase of the syndrome that Kraepelin referred to as periodic catatonia appears similar in many ways to the phenomenon currently termed “delirious mania.” Delirious mania has been described as a nightmarish overac­tive state with acute onset of disorientation, sleeplessness, amnesia, confabulation, frightening perceptual changes, bizarre behavior, agitation, echophenomena, rambling and often incoherent speech with flight of ideas sometimes alternating with short periods of mutism, negativism, and automaticity.

Clinical Features and Diagnosis

Signs and symptoms of catatonia are outlined in Table 55-1 (the Bush-Francis Catatonia Rating Scale). Catatonia may be caused by a host of syndromes ( Boxes 55-1, 55-2, 55-3, and 55-4 ). Efforts should of course be made to identify the etiology of catatonia and treat it, if possible.