Abstract
Catatonia is a phenomenon that has been well recognized and described but for which the pathophysiology remains largely a mystery [1]. It has long been recognized as a feature of either a schizophrenic illness [1, 2], severe mood disorders [2, 3] or periodic catatonia disorder [4]. Several metabolic, neurological, psychiatric, and toxic conditions including neuroleptic malignant syndrome or extrapyramidal syndrome can cause catatonia [5–10] and it is defined predominantly by a constellation of motor symptoms [11]. The features of extreme negativism, motor immobility, agitation, muteness, and posturing are well described and constitute the criteria for diagnosing catatonia under DSM-IV [12]. Although it can occur in the setting of other recognized psychiatric illnesses, it is always distinguished by characteristic signs and symptoms, and it has been proposed that it should be classified separately from other psychiatric diseases [1]. Treatment for schizophrenia patients with recurrent catatonia from the perspective of recurrence rate has rarely been reported. Although acute catatonia has been shown to be responsive to benzodiazepines, they are generally not effective for chronic catatonia. A double-blind placebo-controlled study shows that lorazepam has no effect in chronic catatonia [13]. We report a patient who had recurrent catatonia that was unresponsive to most anti-psychotics but responded to high doses of lorazepam and needed long-term lorazepam for maintenance.
Case Report
A 28-year-old Caucasian woman with nil contributory family and past history presented with an 8 month history of volitional disturbance, emotional blunting, and social withdrawal, along with increasing refusal to talk or eat food, for which she was admitted to the female unit of the psychiatric institute at Central Institute of Psychiatry, Ranchi, India. It was noted that for the last 6 months she had been constantly keeping quiet and was difficult to engage in conversation. There were occasional brief periods when she became extremely excited and would resort to unprovoked aggression. She needed close supervision by a full-time caregiver. She was drug naïve on admission.
At interview, complete mutism was evident, along with staring and withdrawal. She sat still, staring vacantly into space, making no eye contact with others, and maintaining the same. She would look up on response to the examiner's speech but would utter no words. She was able to follow instructions but was difficult to engage in conversation and would quickly return to her downcast posture. On serial interviews she admitted to being frightened and being extremely anxious when in catatonia. However, no hallucinations were ever elicited. A proper cognitive assessment was not possible. A provisional diagnosis of catatonic schizophrenia was made, keeping in view her catatonic symptoms and negative symptomatology once catatonia had abated. Although she did not meet strict diagnostic criteria for catatonia of Rosebush et al. [14] and Lohr and Wisenewski [15], she had four of the 14 catatonic signs on the Bush–Francis Catatonia Screening Instrument: staring, mutism, posturing and withdrawal, and two or more signs were considered sufficient for the diagnosis of catatonia [16].
She was started on lorazepam 4 mg day–1 in divided doses. Significant reduction in her catatonic symptoms was noted within 3 days. Her mutism and withdrawal were considerably reduced. She could be engaged in conversation. Olanzapine 10 mg day–1 was then added. Five days after lorazepam was started, catatonic symptoms were no longer evident and she had a conversation with her guardians (not possible for some months). Gradual improvement in her social interaction, cognitive functioning and her speech continued in the following 3 weeks.
A reduction of her lorazepam to 2 mg day–1 was quickly followed by recurrence of catatonic symptoms and withdrawal; she again responded promptly to an increase of her lorazepam to 4 mg day–1. With her catatonic symptoms abated, a picture of predominantly negative symptoms became apparent. Extensive investigations, including biochemistry, hematology and quantitative electroencephalogram showed no significant abnormality. When lorazepam was tapered and stopped, it led to a recurrence of catatonic symptoms and withdrawal, which happened five times in 6 months and every time the patient promptly responded to lorazepam, this time in higher doses, up to 6 mg day–1. Adequate trials of olanzapine, haloperidol and risperidone failed to alleviate her catatonic symptoms. She was then given an adequate trial of clozapine up to 300 mg day–1, but so far she has been non-responsive. She would always respond to the addition of lorazepam, irrespective of the antipsychotic used. She is now being maintained on lorazepam 4 mg day–1 in divided doses and has achieved near-premorbid functioning.
Discussion
The DSM-IV describes three forms of catatonia: medical catatonia, in which a systemic disease is implicated; catatonic schizophrenia; and catatonia as a modifier for a major affective disorder [12]. Two of the following five criteria are required: motor immobility, excessive motor activity, extreme negativism or mutism, peculiarities of voluntary movement, and echolalia or echopraxia. We, however, believe that the present patient met the criteria for a diagnosis of catatonia without any psychiatric or medical disorder, or in other words, idiopathic catatonic disorder. However, the present nosology unfortunately did not permit a diagnosis of idiopathic catatonic disorder. Other diagnoses were not considered due to lack of family history and due to normal biochemistry.
The concept of idiopathic catatonia can be explained by the neurochemical hypothesis, initially proposed by Northoff in 2002 [17], which focuses on four neurotransmitters: dopamine (DA), γ-aminobutyric acid (GABA), glutamate, and serotonin (5-HT). Evidence points to a central role for GABA, with downregulation of GABA (A) receptors. In fact, the GABA-A receptor agonist/modulator lorazepam successfully treats 60–80% of all acutely catatonic patients and is also effective in chronic recurrent catatonia, as was evident in the present case. Northoff also suggested that motor and affective symptoms might be more amenable to GABA agonists than are behavioral symptoms, which may be affected by an altered relationship between GABA-ergic and glutamatergic neurotransmission [17].
The efficacy of benzodiazepines in the treatment of acute catatonia is well-documented [14, 16, 18]. There have, however, been case reports of chronic catatonia with positive responses to benzodiazepines [19, 20]. The catatonic symptoms in the present case, although persistent for 14 months and refractory to other treatments, responded promptly to lorazepam, suggesting that benzodiazepines may be useful in some cases of recurrent catatonia. Electroconvulsive therapy was not considered due to the same reasons. Although catatonia has been shown to be responsive to antipsychotics [21–23], its failure in the present patient and responsiveness only to maintenance lorazepam suggests that a certain group of patients may require long-term treatment with lorazepam, especially those who may have downregulation of GABA-A receptors [17].