Prashant Tibrewal

Clinical predictors of response to treatment in catatonia

OBJECTIVE This study aims at identifying predictors of treatment response to lorazepam in catatonia. METHODS The clinical charts of 107 inpatients, admitted over duration of 2 years, with a primary diagnosis of catatonia were examined for response to lorazepam trial. Trial was considered as having received 3-6 mg per day of lorazepam for at least 3 days. RESULTS Out of these 107 patients, 99 received lorazepam and 8 received electroconvulsive therapy as the first line of management. There were 32 responders and 67 nonresponders to lorazepam. The nonresponders were characterized by rural background (85.1% vs. 62.5%, P=.01), longer duration of catatonic symptoms (108.88 vs. 25.12 days, P=.018), mutism (63.6% vs. 31.3%, P=.02) and presence of first-rank symptoms like third-person auditory discussing-type hallucinations (16.4% vs. 12.0%, P=.03) and made phenomena (7.5% vs. 0%, P=.04). The presence of waxy flexibility (12.5% vs. 4.5%, P=.03) predicted good response. CONCLUSIONS This study identifies that longer duration of illness, presence of catatonic sign of mutism and certain specific phenomena like third-person auditory hallucinations and made phenomena predicted poor response to lorazepam in catatonia. This could provide insight into the prediction and planning of the appropriate treatment strategies in this psychiatric emergency.

Response rate of lorazepam in catatonia: A developing country's perspective

BACKGROUND Catatonia is a syndrome characterized by concurrent motor, emotional, and behavioral symptoms. Short-term benzodiazepine administration and electroconvulsive therapy have proven to be safe and useful for treatment of this syndrome. AIMS This study aimed to explore the evidence of effectiveness of lorazepam as a first line treatment for catatonia in a tertiary psychiatry centre in India given the lack of facilities for ECT in primary care centers of developing countries. We examined the response rate of lorazepam in Catatonia. METHODOLOGY Clinical charts of 107 inpatients, admitted over a duration of two years, with a primary diagnosis of catatonia were examined for response with lorazepam trial. Trial was considered as having received 3-6 mg per day of lorazepam for at least 3 days. RESULTS Among the patients who were given lorazepam treatment, 32 out of 99 (32.3%) showed response (with complete resolution of catatonic symptoms). Improvement in catatonic symptoms was seen in 68 out of 99 (68.7%) patients. CONCLUSIONS Lorazepam is cost effective and could rapidly relieve catatonic signs, even without the use of ECT in a significant proportion of catatonic patients. Its early use can prevent disease progression and complications.

Could modafinil be a drug of dependence

Modafinil is a novel, nonamphetaminebased wake promoting medication approved for narcolepsy and obstructive sleep apnoea. Owing to its activating and cognitive enhancing effects, there is an expanding list of off-label use, including the treatment of methamphetamine and cocaine withdrawal. Although modafinil was previously thought to be nonaddictive (Jasinski, 2000),we present a possible case of modafinil dependence. Mr A is a 23-year old man prescribed modafinil 200 mg for 6 weeks as an adjunctive treatment for daytime hypersomnolence and fatigue following methamphetamine withdrawal. The patient was admitted 6 months later with a methamphetamineinduced psychosis. It was discovered Mr A had also been abusing modafinil at a self-increased dose of 400 mg daily. His psychosis resolved and modafinil was to be ceased owing to lack of evidence in the long-term treatment of methamphetamine withdrawal. Mr A became extremely agitated regarding the planned cessation. He stated that since commencing modafinil, his chronic methamphetamine use had decreased significantly from daily to episodic use. He spoke positively about modafinil helping him concentrate, feeling energised and becoming more productive. Mr A’s accounts were contrary to the history provided by his parents, who attributed his daily modafinil use as the cause for his recent difficulties in social and occupational functioning. Following protracted discussions, Mr A reluctantly agreed to cease modafinil and did not experience any withdrawal symptoms. In our opinion, Mr A satisfied the DSM 5 criteria for substance abuse disorder as highlighted by his psychological craving, unwillingness to cease use, social and occupational impairment, risky use, self-initiated increase in dose and continued attempts to source modafinil. Our literature search identified only one report of modafinil dependence in a patient with schizophrenia taking supratherapeutic doses of 2000 mg daily for 12 months (Kate et al., 2012). At a neurobiological level Volkow et al. (2009) demonstrated that modafinil exhibited a dose-dependent inhibition of dopamine transporters. This action reduces reuptake of dopamine and increases synaptic dopamine concentrations, particularly within the nucleus accumbens, an essential component in the biological pathway of addiction. This case highlights the potential of modafinil to be a drug of dependence. On this basis, clinicians should adopt a cautious approach when prescribing modafinil, especially in patients with a known history of substance abuse problems. Further clinical and basic science research is warranted focusing on its potential for abuse and dependence.

St John’s wort – Is it safe in Bipolar Disorder?:

Australian & New Zealand Journal of Psychiatry, 49(12) members reported changes in her behavior in the form of increased talkativeness, cheerfulness, increased physical activity and increased religiosity. The patient was evaluated on the Naranjo Adverse Drug Reaction Probability Scale, and the score was found to be 6, which was suggestive of ‘probable’ adverse drug reaction. Opipramol was stopped immediately and olanzapine 15 mg/day was commenced. Her symptoms responded to this medication. There is one reported case of opipramol-induced mania in the literature (Firoz et al., 2015), our case being the second. In the first case report, the patient was suffering from Bipolar Depression and switched into mania on opipramol. The propensity of antidepressant-induced mania is lower in anxiety disorders than that in bipolar disorder treated with tricyclic compounds. Despite being different from conventional tricyclic antidepressants (TCAs), opipramol still carries the risk of switching to mania; hence, adequate caution needs to be exercised.

Agomelatine-Induced Akathisia in a 38-Year-Old Woman With Depression

To the Editor: Akathisia is linked to dopamine deficiency most often associated with antipsychotic medication. Newer antipsychotic medication is thought to reduce akathisia due to its serotonin (5-HT) 2(2A/2C) receptor blockade activity.1 Akathisia may also be related to increased adrenergic neurotransmission.2 Mirtazapine in low doses (15 mg) is a 5-HT 2A/2C antagonist and is antiakathisic, while in higher doses (> 30 mg/d) it may induce akathisia due to stimulation of adrenergic neurotransmission via alpha2 autoreceptor blockade.2 Agomelatine is a novel antidepressant that is both a melatonergic agonist and a 5-HT 2C antagonist.3 Agomelatine also enhances dopaminergic and adrenergic input to the frontal cortex. There is 1 previous report of agomelatine-induced akathisia with concomitant duloxetine treatment.4 That report suggested a pharmacodynamic drug-drug interaction causing noradrenergic overstimulation as an explanatory model.4 We present a novel case of likely agomelatine-induced akathisia. Case report. Ms A is a 38-year-old woman who presented with a several-month history of depression without anxiety or suicidal ideation. Many years previously, she had been prescribed sertraline without experiencing akathisia. There was no significant past medical history. Agomelatine was started at the first visit at a dose of 25 mg. Immediately after starting agomelatine, Ms A noticed an inability to sit still, restless movement of the legs, and a constant urge to move. Over the ensuing weeks, she became more significantly distressed and experienced insomnia, loss of appetite and weight, and suicidal ideation. After 5 weeks of taking agomelatine, a psychiatric consultation was sought and a provisional diagnosis of agomelatine-induced akathisia was made on the basis of a global Barnes Akathisia Scale5 score of 4 (marked akathisia). Within 3 days of stopping agomelatine, Ms A noticed significant improvement; in 5 days, all symptoms of akathisia had ceased with no ongoing anxiety, insomnia, or suicidal ideation. In this case, agomelatine was likely causing akathisia on the basis of a Naranjo Adverse Drug Reaction Probability Scale6 score of 7 (probable adverse drug reaction). This case is the first report without a concomitant drug-drug interaction. The induction of akathisia by agomelatine in this patient was somewhat unexpected, given that agomelatine is a 5-HT 2C antagonist and increases dopamine transmission in the frontal cortex. However, there is debate as to whether 5-HT 2A antagonism is more related to antiakathisic effect as opposed to 5-HT 2C antagonism. It may be that an increase in adrenergic stimulation induced by agomelatine may cause akathisia. However, akathisia is a complex phenomenon, and a clear explanatory model for what we observed is unknown. Clinicians should therefore be alert to the possibility of akathisia in patients prescribed agomelatine.

Cogan's syndrome and treatment-resistant psychosis.

Cogan’s syndrome (CS) is a rare autoimmune disease, characterised by ocular disease, interstitial keratitis and vestibuloauditory dysfunction with 10% developing visual impairment and 52% developing hearing loss, which is typically bilateral and progressive (Gluth et al., 2006). Mr K is a 46-year-old man diagnosed with CS in 2011 after developing anterior uveitis and hearing loss. He was treated with Prednisolone, topical corticosteroids and the immunosuppressant mycophenolate but still developed bilateral sensorineural hearing loss and significant visual impairment. Mr K was diagnosed with autism and intellectual disability as a child. Since 1991, Mr K experienced psychotic episodes consisting of ‘bad thoughts’, obsessional behaviours, images of Jesus in his mind together with non-specific paranoid ideation. He maintained remission on a combination of Olanzapine and Flupenthixol Decanoate. However, following CS onset, his psychosis progressed accompanied by new-onset auditory and visual hallucinations with more persistent and severe persecutory delusions. Mr K was subsequently commenced on Clozapine, and this led to significant improvement with residual visual and auditory hallucinations. In the published literature, there have been 250 cases of CS and only two cases associated with psychosis (Gluth et al., 2006; Raese and Ibrahim, 2015). There is an established late paraphrenia literature describing the role of sensory impairment in the development of psychosis in later life (Osvaldo et al., 1995). There is evidence to suggest that pre-existing brain conditions might play a role in the development of late-onset psychosis (Raese and Ibrahim, 2015). Given Mr K’s autism, intellectual disability and previous psychotic episodes, it is possible that these pre-existing conditions resulted in him developing treatment-resistant psychotic symptoms. In addition, the different phenomenology and treatment resistance following onset of CS could be directly associated with CS, the sensory loss secondary to CS or due to a combination of these factors and his autism. Currently, the link between CS and psychosis is not well established. Given the low prevalence of CS, it is possible that an association between CS and psychosis has yet to be established. Possibly, this case may add to the increasing evidence of a link between the autoimmune conditions and schizophrenia. This case also suggests that the onset of sensory impairment in people prone to psychosis may lead to worsening of preexistent psychosis, different phenomenology (in particular perceptual disturb ances) and treatment resistance.

Electroconvulsive therapy and type 1 Chiari malformation

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Parenteral lorazepam's unavailability in Australia and the impact for catatonic patients.

Catatonia is often under-recognized and undertreated in medicine. Delays in effective evidence-based treatment can lead to significant complications. Mr X, a 65-year-old man with a mild intellectual disability and no past psychiatric history, presented with abrupt onset catatonic symptoms consisting of immobility, decreased responsiveness and negativistic phenomena. He was hospitalized and an organic etiology was strongly considered given a positive venereal disease research laboratory (VDRL) test, delaying the diagnosis of catatonia by 6 weeks. Following diagnosis of catatonia, 6 mg/day of oral lorazepam and 3 mg/day of subcutaneous clonazepam was trialed for 2 weeks with little beneficial effect. He was subsequently transferred to a tertiary hospital for electroconvulsive therapy (ECT). At presentation, his Bush-Francis Catatonia Rating Score was 21. Mr X required a protracted course of ECT (19 bilateral) to achieve sustained response. Once treatment ended, he exhibited an elevated mood, confirming bipolar disorder as the etiology for his catatonia. He developed complications due to his prolonged immobility and posturing, including deep vein thrombosis and significant muscle contractures. The delayed response to ECT is likely related to his prolonged catatonia presentation being initially misdiagnosed and inadequately treated prior to commencing ECT. Duration of catatonic symptoms is an indicator for ECT response (Narayanaswamy et al., 2012). The use of oral benzodiazepines and lack of availability of parenteral lorazepam possibly prolonged his episode of catatonia and contributed to the development of complications and delayed ECT response. Parenteral lorazepam is the recognized first-line treatment for catatonia with response rates between 67% and 79% (Sienaert et al., 2014), and occurring usually between 3 and 7 days (Tibrewal et al., 2010). Oral benzodiazepines including oral lorazepam have been less studied in the literature in catatonia compared to the parenteral formulation. It is concerning that parenteral lorazepam is not readily available in Australia. Severe catatonia often results in patients unable to take oral medications, essentially leaving parenteral medication as the only available first-line intervention before proceeding to ECT. Currently, parenteral lorazepam is only available through a formal submission to the Special Access Scheme with local ethics approval required and a registry of prescribers listed with reports submitted annually. These significant barriers and lack of supply of parenteral lorazepam in Australia through pharmaceutical companies suggest catatonia might not be appropriately or adequately treated. It may also result in over-utilization of ECT. The authors would suggest that the Therapeutic Goods Administration be approached with modifications made to enable parenteral lorazepam to be readily available for clinicians to use in treating catatonia.

Schizoaffective disorder, catatonia and white matter changes – Revisiting the microglial hypothesis

A previous retrospective study reported that antidepressant treatment with escitalopram, a selective serotonin re-uptake inhibitor (SSRI), significantly reduced the platelet count, whereas bupropion, a noradrenalin and dopamine re-uptake inhibitor (NDRI) had no such effect (Song et al., 2012). Whether escitalopram-related thrombocytopenia can be reversed without discontinuing anti-depressant therapy, such as by using bupropion as an alternative drug, is unclear. Herein, we describe the case of a 31-year-old physically healthy and drug-naïve Taiwanese male who received anti-depressants for depressed mood (initial Hamilton Depression Rating Scale [HAM-D] score 28). Before treatment, his haematological findings were all within normal ranges, including a platelet count of 159,000/μL (reference range: 150,000–400,000/μL). However, after 1 month of monotherapy with escitalopram (10 mg/day), his platelet count decreased to 106,000/μL despite other haematological profiles remaining normal. Neither medical disease nor traumatic injuries were noted during the treatment period. Inflammatory, liver and thyroid functions were all within normal limits, as were coagulator parameters including pro-thrombin time and partial pro-thrombin time. In addition, no increased bleeding tendency signs such as unexplained bruising or petechiae were noted. Due to concerns over the possible side effects of escitalopram, treatment was shifted to bupropion monotherapy (150 mg/day). After 2 weeks of bupropion treatment, follow-up haematological studies showed an increase in platelet count to 136,000/μL, which increased to 157,000/μL after 1 month of treatment. His depressed mood improved (HAM-D score 13), and other haematological profiles remained normal throughout. By excluding the presence of other aetiological factors that may have contributed to thrombocytopenia, the cause of the adverse haematological effect seems attributable to escitalopram. A previous case series of fluoxetine, another SSRI, reported that thrombocytopenia associated with treatment reversed after the agent was switched to reboxetine, a noradrenalin re-uptake inhibitor (NRI) (Yucel et al., 2015). This is consistent with our patient in that escitalopram-related thrombocytopenia was reversed after shifting the antidepressant to the non-SSRI bupropion. Although the definite biological mechanism for this phenomenon is unclear, drug-induced immune thrombocytopenia has been demonstrated with a probable level of evidence (Aster and Bougie, 2007). Taken together with our findings, both NRIs and NDRIs can be considered as alterative agents for SSRIrelated thrombocytopenia if ongoing anti-depressant therapy is needed. Our findings provide clinicians with a potential treatment strategy if SSRIrelated thrombocytopenia occurs. Further clinical and pharmacological studies should be considered to validate our findings.

Successful clozapine re-challenge following myocarditis:

Objective: To explore the evidence around clozapine re-challenge following myocarditis. Conclusion: This case adds to the 17 cases of clozapine re-challenge following myocarditis, of which 71% were successful (12 cases). This demonstrates that re-challenge could be performed safely and effectively in the context of clozapine-induced myocarditis, if accompanied by a strict and rigorous monitoring protocol.