Clozapine responsive catatonia: A series of five cases.

The main objective of presenting the case series is that despite dramatic symptomatic response by intra venous lorazepam or electro convulsive therapy irrespective of primary diagnosis in catatonia cases some cases remain difficult to treat by conventional treatment. Here, we present five catatonia cases who did not respond to conventional treatment even when treated for primary psychiatric diagnosis along with treatment for catatonia. They ultimately responded partially or completely to clozapine only, which explains the multi-factorial causation of catatonia syndrome as postulated by different scientific research.

The concept of catatonia was first described by Kahlbaum (1874).[1] Catatonia is a syndrome characterized by several psychomotor abnormalities and encompasses a broad range of organic and non-organic causes.[2] There are several postulated causes of catatonia, e.g., “top down modulation” of basal ganglia due to deficiency of GABA,[3] hypoactivity of excitatory neurotransmitter glutamate[4] or sudden blockage of dopamine.[5] The current frequency of catatonia in psychiatric hospitals of India is 13.5%.[6] The incidence of catatonia has decreased all over the world due to improved diagnosis and modern treatment.[7] Moudsley recommends treatment initiation with injectable lorazepam which have a general response rate of 80-83%.[89] Electro convulsive therapy (ECT) is the next option and used to treat emergency condition like lethal catatonia or catatonia with complications.[8] Other options include treatment with other atypical antipsychotic (e.g., olanzapine, quetiapine, clozapine), carbamazepine, memantine (NMDA antagonist), amantadine (decreases glutamate).[2] Catatatonia has a recovery rate of 12-40% regardless of treatment administered.[10] Adolescents and delay in treatment carry poorer prognosis.[11]

Dopamine D2 hypoactivity, glutamate N-methyl-D-aspartate (NMDA) hyperactivity, or Gama amino butyric acid (GABA) hypoactivity are believed to cause catatonia.[12-14] Second generation anti psychotic (SGAs) can provide marked improvement in patients with catatonic schizophrenia.[15] Salokangas et al.[16] note that “atypicals” pass more dopamine to the D2 receptor when dopamine is low in the basal ganglia. This suggests that SGAs with low D2 binding – such as clozapine, olanzapine, and quetiapine – are more beneficial than other SGAs for catatonia. Serotonin binding or other mechanisms might add to these drugs’ anticatatonic effect.[14] There are case reports which indicate that clozapine is effective in cases of catatonia[1718] though till now it is not recommended in any guideline of treatment of catatonia.

We present this interesting series of five cases which we came across in our inpatient setting at the Department of Psychiatry, Medical College, Kolkata during the period February 2010-January 2011. They did not respond, rather deteriorated, to conventional treatment of catatonia and regardless of primary diagnosis responded partially or completely to clozapine only.

CASE REPORTS

Case 1

A 14-year-old Hindu, female patient from urban background, middle socio-economic class, studying in class eight presented with intermittent non-goal directed excitement, rigidity, low-grade fever, posturing, occasionally psychological pillow like symptom, waxy flexibility, mannerism, verbal stereotypies following an attempted rape by a neighbour. After detailed history, mental state and neurological examination and relevant detailed investigations the provisional diagnosis was made to be catatonia in a case of psychosis not otherwise specified (NOS) (DSM IV).

Case 2

A 15-year-old Hindu male patient from middle socio-economic class, urban background, education up to class tenth, presented with history of recurrent catatonia precipitated every time by some significant or insignificant emotional factor in family or school for the last 5 years. This episode was characterized by stupor, rigidity, incontinence of urine, mutism, posturing, smiling without apparent reason and occasional excitement. Each of the three past episodes persisted for 4-6 months, with similar kind of catatonic symptom and did not respond to lorazepam, ultimately resulted into complete recovery. He never received any SGA due to these symptoms. After detailed history, mental state and neurological examination and relevant detailed investigations the provisional diagnosis was made to be major depressive disorder recurrent with catatonic feature current episode severe depression with psychotic and catatonic feature (DSM IV).

Case 3

A 56-year-old Hindu male patient from middle socio-economic class, urban background, education up to MA, school teacher by profession presented with recurrent catatonic symptom of mutism, rigidity, posturing, waxy flexibility and nihilistic delusion. Each of the five past episodes (1st being at the age of 40 years) persisted for 4-6 months, with similar kind of catatonic symptom and did not respond to lorazepam or ECT. After detailed history, mental state and neurological examination and relevant detailed investigations the provisional diagnosis was made to be catatonia in a case of mood disorder currently severe depression with psychotic feature (DSM IV). Each episode persisted for several months to years followed by complete recovery spontaneously.

Case 4

A18-year-old male, Hindu patient from lower socio-economic class, educated upto class 12th presented with history of non-goal directed excitement, mannerism, stereotypies, rigidity and posturing for last ten days. He was diagnosed to be a case of catatonia in a case of cannabis dependence (DSM IV).

Case 5

A 25-year-old female, Hindu patient from lower socio-economic class, educated upto class sixth, home maker, presented with history of mutism, staring look, rigidity, waxy flexibility and posturing for last seven days. We diagnosed her as a case of catatonia due to unknown cause. All the patients did not have any history of convulsion, seizure, head injury, high fever, dog bite or any other feature suggesting organicity. None was on any treatment prior to admission.

Keeping aside the primary psychiatric diagnosis all the patients were given an uncommon treatment protocol to treat catatonic symptoms first. The protocol was as given below:

Admission in psychiatry ward

Investigations

Clinical-pulse, blood pressure (BP), temperature, hydration status, neurological examination, Kayser Fleischer (KF) ring

Laboratory-Hemoglobin (Hb), total leucocyte count (TLC), differential leucocytes count (DLC), urea, creatinine, fasting blood sugar (FBS), liver function test (LFT), Na+, K+, urine routine and microscopy, X-ray chest, electrocardiogram (ECG), magnetic resonance imaging (MRI) brain, creatinine phosphokinase (CPK)

Psychological-Busch Francis Catatonia rating scale (BFCRS).

*All the above mentioned investigation reports were non-contributory for all five patients except BFCRS scores which were 30, 32, 29, 24, 22, respectively for the above mentioned patients during admission.

Treatment

IV Lorazepam up to 12 mg/day in divided doses starting from 3 mg/day in divided dose

If not controlled by lorazepam in next 5-7 days they were given ECT (bipolar) in thrice weekly schedule for at least five ECT

If not controlled by ECT they were given upto 15 mg/day of IM or mouth dissolving olanzapine for atleast two weeks

Depending on the primary psychiatric diagnosis Case 2 received fluoxetine up to 40 mg/day from beginning, Case 3 received venlafaxine up to 225 mg/day after ECT failed to improve the patient and still the patient is taking venlafaxine

When not controlled by the above regimen clozapine in a gradually titrating dose upto 300 mg/day with proper hematological monitoring was instituted either alone or with SNRI in the third case or SSRI in second case.

All the five patients responded either completely (Case 5 and 4) or partially (Case 1, 2, and 3) to clozapine in next 2-4 weeks. The BFCRS score came down to 5, 4, and 8 respectively for the first three cases. The first case was lost to follow up. The second case improved completely in next two follow up and was completely alright in third follow up as also Case 4 and 5. The third case maintained a near complete recovery with BFCRS score four in third follow up. Clozapine was tapered off in Case 4 and 5 after one month time and still they maintained well. None developed any serious side effect except transitory tachycardia in Case 1, 3, and 4 which resolved after few days.

CONCLUSION

In the present report almost all patients were treated finally with clozapine and there was no further recurrence of catatonia for six months. Although lorazepam and ECT have been shown to produce a good response in catatonia, some patients still require antipsychotic drugs such as clozapine for their psychotic symptoms, to prevent recurrence of catatonia. Studies also show the effectiveness of clozapine in catatonic schizophrenia as well as organic catatonia.[1718] Further studies should examine the effectiveness of clozapine for treatment of catatonia.