CASE HISTORY

HA is a 16 yr old boy from Afghanistan who first came to the attention of mental health services after he had cut off the tip of his nose. He had apparently responded to voices which commanded him to do so. The voice of God also told him to kill himself and then his mother and siblings who were at the time in Afghanistan.

English is not HA’s first language and this made communication difficult without the help of an interpreter. He seemed generally preoccupied and he said his mind was not under his control. Collateral information from his cousins revealed that he had become unwell six months earlier. He began to isolate himself, there was a gradual deterioration in his self care and he was paranoid. He believed the police were against him; he thought Afghans were conspiring with the police to plot his transfer to Afghanistan via the immigration services.

At the initial assessment, his face was partially covered with a bandage and he looked confused and puzzled. His speech lacked spontaneity (responding with short answers) and he seemed low in mood. He was clearly thought-disordered, admitting to hearing voices, and lacked any insight into his illness.

Given his history of emigration to the UK (a stressful life event), cannabis and heroin use (as shown below), lack of family and social ties, access to a lethal weapon (a knife), admission to a psychiatric hospital for a mental illness (paranoid schizophrenia with command hallucinations) and being male, he was at risk of suicide. Although he was thought disordered, at interview he was reasonably cooperative and there was no evidence of aggression or violence towards at the time.

Routine blood tests did not reveal any significant findings. The physical examination revealed the loss of the distal 2 cm of his nose and swelling of his right hand possibly due to thrombophlebitis. He was prescribed some flucloxacillin (500 mg QDS for seven days) for a wound infection. Urine drug screen on admission showed cannabis. HA later admitted to extensive cannabis and occasional heroin use in the past.

During his first week, HA showed evidence of bradyphrenia (thought retardation), poverty of speech, anhedonia and anxiety related to his immigration status. There was no history of physical abuse; he remained guarded with delusions of persecution. He was initially commenced on aripriprazole at 10 mg daily and 10 mg bd after one week.

By the second and third weeks, he was head banging, eating faeces in the toilet, showing some ambitendency and was not socializing or engaging in ward activities. There was no response to aripriprazole after 4 weeks. He ate less; remained guarded with delusions of persecution; self neglect and anhedonia. Aripiprazole was changed to risperidone. His blood tests were repeated and the dose of risperidone was gradually increased to 3 mg bd, over a 4 week period. A depressive disorder was considered as part of the differential diagnosis but antidepressant treatment was delayed awaiting antipsychotic response.

Following the introduction of risperidone, there was deterioration in his condition with a much more pronounced motor disorder and the appearance of catatonia. He showed a severe reduction in his physical activity, mutism, mild cog wheeling, waxy flexibility including the ‘psychological pillow’ and ambitendency. He scored 22 on the Bush Francis Catatonia Rating scale (Bush et al. Reference Bush, Fink, Petrides, Dowling and Francis1996a). He had a pulse rate variation of 86 to 120; his other vital signs were normal.

For further diagnostic purposes he was challenged with 2 mg intravenous lorazepam. Within 5 minutes of its administration, HA began to smile (rather infectiously); got out of bed with verbal encouragement; engaged in ward activities and spontaneously remarked, ‘I am ready for dinner’. His underlying mood state was not depressed. He continued on oral lorazepam (2 mg bd) and risperidone for 7 days.

He responded well initially to lorazepam for a couple of days but deteriorated afterwards and remained psychotic with paranoid and persecutory delusions. After one week, lorazepam was swapped to 5 mg diazepam qds; the dose was increased after one week to 10 mg qds. There was only a partial improvement in his catatonic features after 5 to 6 weeks of diazepam.

It would appear that the improvement in HA’s catatonia unmasked the true extent of his psychotic symptoms. He head banged and threatened violence to others requesting to leave the ward for Afghanistan. In view of his initial action of nose cutting, HA was viewed as high risk of violence to himself and others and the doses of his anti-psychotic medication and p.r.n. haloperidol was increased despite sedation and the potential risk of worsening his catatonia or provoking a neuroleptic malignant syndrome. The dose of risperidone was tapered and discontinued after 6 weeks.

He also developed oral candidiasis which was treated with nystatin drops. A neuropsychiatric presentation of HIV was considered and he undertook a retroviral screen for HIV and for hepatitis. His HIV screen was negative but he was positive for hepatitis B. We assume that his candidiasis was secondary to poor oral hygiene related to his restricted movement. He continued to express paranoid delusions about being deported to Afghanistan and auditory hallucinations about a certain ‘Abijaan’. He was then commenced on clozapine.

Over a twelve week period following the introduction of clozapine, his catatonic features have improved significantly. His psychotic symptoms became better controlled and he began to eat and drink, evidenced by some weight gain. He was also more spontaneous in his speech and in his interaction with other peers on the unit.

The doses of diazepam and haloperidol were tapered and stopped over four weeks. He remained on 125 mg bd clozapine. He has remained stable on the present dose. He has remained well on clozapine for the past 12 weeks. His latest creatinine kinase was normal at 142 U/L. He scored 2 using the Bush Francis Catatonia Rating scale for a repeat check of his catatonic features after 10 weeks (scoring 1 on rigidity and 1 in occasional pulse variation). After 4 months on clozapine therapy all catatonic symptoms including rigidity have resolved.

DISCUSSION

In contrast to catatonia in adults where the presentation is commonly associated with an underlying affective disorder, children and adolescents have higher rates of psychotic disorder and schizophrenia (Dhossche & Bouman, Reference Dhossche and Bouman1997; Rogers, Reference Rogers1991). There is a need for further research in the area of schizophrenia complicated by catatonia in adolescents as it appears to be a clinically relevant but understudied subgroup (Cohen et al. Reference Cohen, Nicolas, Flament, Périsse, Dubos, Bonnot, Speranza, Graindorge, Tordjman and Mazet2005, Reference Cohen, Flament, Dubos and Basquin1999).

Various authors may suggest that neuroleptic malignant syndrome (NMS) and neuroleptic-induced catatonia (NIC) are part of the same neuroleptic-toxicity spectrum NIC being an initial stage of the progression to NMS (Woodbury & Woodbury, Reference Woodbury and Woodbury1992). The literature also reveals a lack of consensus regarding the classification of catatonia; some arguing it to be part of a neuroleptic malignant syndrome and others argue it is a subtype of schizophrenia and perhaps a separate clinical entity.

We support the view held by Taylor & Fink (2003) that catatonia is an independent syndrome with the following subtypes: non-malignant, delirious and malignant. The non-malignant type refers to the classic features first described by Kahlbaum, the delirious type includes delirious mania, and the malignant type includes lethal catatonia, neuroleptic malignant syndrome and serotonin syndrome (Rajagopal, Reference Rajagopal2007).

Intravenous barbiturates were first demonstrated to be effective in the treatment of catatonic stupor in 1930 but were replaced by benzodiazepines (BZDs) in the 1970s. BZDs have been shown to have an approximately 70–90% positive response rate for the treatment of retarded catatonia, (Bush et al. Reference Bush, Fink, Petrides, Dowling and Francis1996b). In 1935, patients with catatonic schizophrenia were reported to recover when treated with chemically-induced seizures. Electroconvulsive therapy (ECT) has now replaced this. ECT is remarkably effective when drugs fail or in patients with malignant catatonia or delirious mania, (Fink, 1999; in Fink & Taylor, Reference Fink and Taylor2002).

The ideal medication is one that is effective, easily administered and has the widest safety margin. Irrespective of the route of administration, low dose BZDs meet the above criteria and have replaced ECT as the first line of treatment for catatonia (Rosebush et al. Reference Rosebush, Hildebrand and Mazurek1992). BZDs may be efficacious in relieving the motor signs of the syndrome but the underlying psychopathology (both psychiatric and medical) remain.

In their review of the pharmacological treatment of catatonia, Rosebush & Mazurek (2004) observed that although the vast majority of patients with catatonia (regardless of the underlying cause) respond robustly to low-dose BZDs, those with schizophrenia have a lower response rate of 20–30%, compared with an overall response rate of 90% in other diagnostic categories. Patients with schizophrenia complicated by catatonia are even less likely to respond (Ungvari et al. Reference Ungvari, Leung, Wong and Lau1994).

Ungvari et al. (2001) comprehensively reviewed the pharmacological treatments of catatonia. Apart from ECT, barbiturates and BZDs, there is limited evidence base to support amantadine, bromocriptine, dantrolene, zolpidem, biperiden, lithium, carbamazepine, thyroid hormone combined with reserpine, clomipramine, and fluoxetine in the treatment of catatonic syndrome.

Antipsychotic medications have been advocated for the treatment of catatonia up until relatively recently (Fink, Reference Fink1994, pp. 276–280). However, some have raised concerns about the emergence of a malignant syndrome (Fink & Taylor, Reference Fink and Taylor2002); possible worsening of the condition (Ungvari et al. Reference Ungvari, Kau, Wai-Kwong and Shing2001) and reports of clinical inefficacy (Cohen et al. Reference Cohen, Flament, Dubos and Basquin1999). Positive treatment outcomes have been noted with haloperidol (Philbrick & Rummans, Reference Philbrick and Rummans1994), risperidone (Kopala & Caudle, Reference Kopala and Caudle1998) and more recently, olanzapine (Melissa et al. Reference Melissa, Delbello, Keith, Foster, Stephen and Strakowski2000).

In the adult literature, clozapine has been found useful both as monotherapy and as an adjunctive treatment. There are four case reports of clozapine used in the successful treatment of catatonia. As an adjunctive treatment, Vattakatuchery et al. (2008) described the case of a woman with treatment-resistant mania and malignant catatonia who did not respond to several of the conventional treatments including ECT but showed a marked response to a combination of clozapine (250 mg daily) and ECT within a few days of initiating treatment.

As monotherapy, Rommel et al. (1998) described the case of a 56 yr old lady who was managed with clozapine for organic catatonia following a frontal lobe injury. Dursun et al. (2005) described two cases of a positive response to clozapine. One was a 49 yr old female with catatonic features accompanied by bizarre delusions who did not respond to several anti-psychotics but to 600 mg daily of clozapine.

The other case of monotherpy with clozapine, (Dursun et al. Reference Dursun, Hallak, Haddad, Leahy, Byrne, Strickland, Anderson, Zuardi and Deakin2005) was that of a 19 yr old male whose illness started two years earlier and who did not respond to psychotropic medication (and a combination of benzodiazepines). The addition of sulpiride, olanzapine and 12 bilateral ECT sessions resulted in minimal improvement in his catatonia. There was a minor improvement in his catatonic symptoms at a clozapine dose of 300 mg per day. The symptoms however resolved when the dose of clozapine was increased to 750 mg daily.

Clozapine is a second generation anti-psychotic (SGA) that is licensed for use in the UK in patients 15 yrs and above (James, Reference James2010) and it is effective against both the positive and negative symptoms of schizophrenia (Kumra et al. Reference Kumra, Kranzler, Rosen, Kester, DeThomas, Kafantaris, Correll and Kane2008), with improvements observed in the first six weeks of treatment.

It appears that clozapine has not always been found to be helpful for catatonia and schizophrenia. We note the contrasting observations that an abrupt withdrawal of clozapine can cause catatonia with stupor due to serotonergic hyperactivity on the one hand (Yeh et al. Reference Yeh, Lee, Cheng, Wen and Chen2004) and an excited catatonia on the other (Lee & Robertson, Reference Lee and Robertson1997). In a case report, Biancosino et al. (2001) described in a 36 yr old woman with disorganised schizophrenia, neuroleptic-induced catatonia following the administration of 250 mg of clozapine.

In our case clozapine was found to be useful both in augmenting the treatment of catatonia in a young person with schizophrenia and in treating the core features of the illness. As far as we are aware, this is the first reported case of a successful management of catatonia complicating schizophrenia with clozapine in an adolescent.

In contrast to the case described by Dursun et al. (2005), HA responded to clozapine at a relatively small dose of 75 mg bd and as early as the first week of treatment. Dursun et al. (2005) argued that the clinical picture in their cases was one of a biphasic response that appeared dose, not time, related. They observed that the dose of clozapine required to improve catatonia was approximately double the doses required to significantly improve psychosis. They also suggest that clozapine monotherapy should be considered an early option, and that dosage should be based on the progress of catatonia, not psychosis.

Although its precise role is unclear, dopamine remains significant as a neurotransmitter in the development of catatonia. Northoff et al. (1997) have postulated a dysfunction in the connections between the glutamate and dopamine systems. Becks et al. (2002, in Dursun et al. Reference Dursun, Hallak, Haddad, Leahy, Byrne, Strickland, Anderson, Zuardi and Deakin2005) have also suggested that at higher doses, clozapine modulates neurotransmitters such as glutamate and/or nitric oxide (dose dependent effects) which in turn improve catatonia.

Our hypothesis is that as there is a resolution of the core psychotic symptoms of schizophrenia with clozapine, there is also a marked improvement in the associated catatonic features. Our observations differ from those of Biancosino et al. (2001). It is likely that children and adolescents respond differently and in a favourable manner to clozapine.

CLINICAL IMPLICATIONS

Morgan et al. (2008) made the point that this ‘often forgotten disorder’ remains poorly recognised and under-diagnosed. Given its fatal potential, it is especially important that clinicians are able to recognise and diagnose the condition especially when it presents outside the remit of a schizophrenic illness as is often the case in adults. The use of appropriate rating scales would aid early detection and treatment of the disorder.

Although BZDs remain beneficial in the relief of motor symptoms associated with the disorder, our case suggests that clozapine can augment the use of BZDs and indeed treat the core psychopathology if a schizophrenic illness is highly likely; as is the case amongst adolescents with catatonia. It is important to stress that close monitoring of clozapine (haematological monitoring; therapeutic levels and side effects) remains paramount as in other patient groups.

CONCLUSION

Catatonia, especially in children and adolescents, remains poorly understood, investigated and under-diagnosed. Although useful in the sharing of clinical experiences and observations, we are conscious of the limited scientific significance of singular case reports; and to this end reiterate the need for further systematic research into the prevalence, treatment, and the response to appropriate treatment of catatonia in children and adolescents.

We acknowledge that the relative lack of conceptual clarity of catatonia as a syndrome and the resulting heterogeneity in treatment studies (Ungvari et al. Reference Fink2010) continues to pose a challenge to the design of appropriate studies to examine the subject area. This is further compounded by the ethical dilemma encountered with treatments involving children and adolescents, especially given the rarity of clinical cases in this age group.