668
ANZJP Correspondence Declaration of interest
with anti-migraine and anti-epileptic medications. Risperidone, olanzapine and clonidine were used without sustained benefit. A trial of escitalopram was initiated following parental request, based on their own investigation on a Rett syndrome Internet forum. An immediate benefit was noted which lasted for 3 months. Head-banging episodes reduced significantly in frequency and duration. She was sleeping for 11 hours each night. Unfortunately, she developed SSRI-induced bruxism. As the escitalopram dose was reduced, bruxism reduced but behavioural issues and sleep disturbances increased. To our knowledge this is the first case report demonstrating the success of escitalopram in managing behavioural problems associated with Rett syndrome. SSRIs may assist through
different mechanisms. Fluoxetine increases MeCP2 expression in rat brains (Chapleau et al., 2013; Pan and Tsai, 2012). SSRIs have been shown to enhance BDNF expression (Chapleau et al., 2013; Pan and Tsai, 2012). Patients with Rett syndrome and mice null for MeCP2 show reduced levels of brain serotonin, thus by adjusting serotonin levels, SSRIs might improve mood and behavioural disturbance (Chapleau et al., 2013; Percy, 2014). Larger animal and human trials are needed to empirically validate the effectiveness of SSRIs in moderating behavioural and sleep disturbance in Rett syndrome.
Written informed consent from the patient’s parents was obtained prior to submitting this manuscript.
Chapleau CA, Lane J, Pozzo-Miller L, et al. (2013) Evaluation of current pharmacological treatment options in the management of Rett syndrome: from the present to future therapeutic alternatives. Current Clinical Pharmacology 8: 358–369. Pan CH and Tsai S (2012) Early intervention with psychostimulants or antidepressants to increase methyl-CpG-binding protein 2 (MeCP2) expressions: a potential therapy for Rett syndrome. Medical Science Monitor 18: HY1–3. Percy A (2014) Rett syndrome: coming to terms with treatment. Advances in Neuroscience 2014: 345270.
Cyclical suicidal ideation following natalizumab infusion for multiple sclerosis Omkar Nagesh1, Tarun Bastiampillai2, Laura Fisher1 and Titus Mohan1
natalizumab infusion for RRMS worsened depressive symptoms in a cyclical pattern. Ms H is a 51-year-old woman with an 8-year history of depression managed with antidepressants and psychotherapy. Ms H was diagnosed with RRMS in 2012 and despite treatment with fingolimod her neurological symptoms progressively worsened. Therefore, 4-weekly (300 mg IV) natalizumab infusions were commenced. Following natalizumab infusions, Ms H noted a cyclical worsening of her depression associated with intense suicidal ideation. Worsening of symptoms began on day 3 post infusion, reaching maximum intensity on days 5–6, and resolving to baseline by day 10. This pattern was consistently observed
after each natalizumab infusion. Beck Depression Inventory (BDI-II) scores were performed post sixth and seventh natalizumab infusions (Table 1). The rate of depression with natalizumab infusions (19%) was not significant when compared to placebo (McCormack, 2013). However a recent report by Mumoli et al. (2013) suggests a causative link between natalizumab and an attempted suicide. Our patient’s cyclical symptom profile, if observed in others, could inform specific high-risk periods necessitating close monitoring of mental state. In addition to its primary action, natalizumab induces peripheral cellmediated inflammation and secretion of cytokines, particularly TNF-α (McCormack, 2013). An association
1Flinders
Medical Centre, Adelaide, Australia Adelaide, Australia
2SAHMRI,
Corresponding author: Titus Mohan, Flinders Medical Centre, Adelaide, South Australia, 5042, Australia. Email: [email protected] DOI: 10.1177/0004867415572414
To the Editor Immune modulating agents have been associated with depression and suicidality (Mumoli et al., 2013). Natalizumab is a monoclonal antibody that slows the progression of relapsing remitting multiple sclerosis (RRMS). Natalizumab blocks the migration of T cells across the blood brain barrier (BBB) preventing further demyelination and plaque formation (McCormack, 2013). We present an intriguing scenario wherein
Consent
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References
Table 1. Beck Depression Inventory (BDI-II) scores following infusions 6 and 7. Infusion cycle Day post infusion
Sixth
Seventh
0
31
31
5
41
42
10
35
33
15
30
29
Australian & New Zealand Journal of Psychiatry, 49(7) Downloaded from anp.sagepub.com at UNIV TORONTO on November 16, 2015
669
ANZJP Correspondence Declaration of interest
between peripheral inflammation and depression has been reported (Postal and Appenzeller, 2015). While peripheral cytokines do not normally cross the BBB, primary afferent nerves, the choroid plexus and specific transporter proteins facilitate cytokine movement from peripheral inflammatory sites to the central nervous system (CNS) (Postal and Appenzeller, 2014). It is possible that transmission of cytokines and other peripheral inflammatory signals to the CNS could be the basis for worsening depressive symptoms and suicidal ideation following natalizumab infusions.
Quantification of peripheral cytokine levels and temporal correlation with severity of depression/suicidal ideation following natalizumab infusions may provide some theoretical basis for the cyclical symptoms demonstrated by our patient. Such correlation, if it exists, also affirms the increasingly recognised role of the immune system in the pathogenesis of depression.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors
McCormack PL (2013) Natalizumab: A review of its use in the management of relapsing-remitting multiple sclerosis. Drugs 73: 1463–1481. Mumoli L, Ciriaco M, Gambardella A, et al. (2013) A possible case of Natalizumab-dependent suicide attempt: A brief review about drugs and suicide. Journal of Pharmacology and Pharmacotherapeutics 4 (Suppl 1): S90–S93. Postal M and Appenzeller S (2015) The importance of cytokines and autoantibodies in depression. Autoimmunity Reviews 14: 30–35.
Risperidone exacerbates Psychosis: A paradoxical phenomenon? Chih-Chao Hsu1*, Chia-Jung Lin2*, Ti Lu1 and Li-Yu Hu1
dosage in a patient with hydrocephalus-induced psychosis. Following shunt surgery for hydrocephalus caused by a posterior fossa arachanoid cyst, a 22-year-old boy experienced auditory hallucinations and persecutory delusions. He had no history of psychotic symptoms or substance abuse before the surgery. We prescribed risperidone (2 mg per day) for the psychotic symptoms. After initial improvement, the symptoms gradually exacerbated 2 years later. No precipitating factor was confirmed during this period. To account for poor drug adherence, 25 mg of longacting injectable risperidone every 2 weeks was prescribed. However, the symptoms worsened and his father attributed this to “side effects from the antipsychotics, especially the longacting injectable one.” Therefore, acute ward admission was arranged 2 months later. Thorough physical examination including brain imaging and blood sampling revealed no active change. His psychotic symptoms with disorganized behavioral disturbance gradually subsided after reducing oral risperidone to 1 mg per day and discontinuing the injectable risperidone. Risperidone was then discontinued entirely and we prescribed flupentixol (3 mg per day) instead. This resulted in a more stable mental condition
without behavioral disturbance within 45 days after admission. Few studies directly mention that risperidone exacerbates psychotic symptoms in hydrocephalus-induced psychosis. However, D2 receptor over-expression in the striatum could possibly be related to psychotic symptoms and behavioral disturbance (Kellendonk et al., 2006). Striatal dopamine D2 receptors are known to be up-regulated in patients with hydrocephalus post the shunting procedure and on long-term risperidone treatment (Nakayama et al., 2007, Tarazi et al., 2001). In conclusion, the synergistic effects of shunting surgery for hydrocephalus in combination with risperidone treatment could have upregulated the levels of striatal D2 receptors and increased the psychosis. Although clinical confounders such as illicit drug use, poor drug adherence, or an inadequate family support system could influence the patient’s condition, the paradoxical effect of risperidone, which to our knowledge has not been reported previously, might explain the clinical presentation of our case. This effect should be considered when selecting antipsychotics for hydrocephalus in patients with psychotic symptoms, especially for long-term use and at higher doses.
1Department
of Psychiatry, Kaohsiung Veterans General Hospital, Kaoshiung, Taiwan 2Department of Nursing, Yuanshan & Su’ao Branch, Taipei Veterans General Hospital, Yilan, Taiwan *Chih-Chao Hsu and Chia-Jung Lin contributed equally to this manuscript Corresponding author: Li-Yu Hu, No. 386, Ta-Chung 1st Road, TzuoYin District, Kaohsiung City, 81362, Taiwan. Email: [email protected] DOI: 10.1177/0004867415574749
To the Editor Hydrocephalus manifests as abnormal accumulation of cerebrospinal fluid and dilated ventricles. These structural changes can induce psychiatric complications, including psychotic symptoms; therefore, antipsychotics are prescribed. However, treatment for hydrocephalus-induced psychosis has not been well investigated and the present choice of antipsychotics is on a case-by-case basis. This letter reports a case of progressive psychotic symptoms concurrent with increasing risperidone
Funding
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
Australian & New Zealand Journal of Psychiatry, 49(7)
Downloaded from anp.sagepub.com at UNIV TORONTO on November 16, 2015
ANZJP Correspondence Declaration of interest
with anti-migraine and anti-epileptic medications. Risperidone, olanzapine and clonidine were used without sustained benefit. A trial of escitalopram was initiated following parental request, based on their own investigation on a Rett syndrome Internet forum. An immediate benefit was noted which lasted for 3 months. Head-banging episodes reduced significantly in frequency and duration. She was sleeping for 11 hours each night. Unfortunately, she developed SSRI-induced bruxism. As the escitalopram dose was reduced, bruxism reduced but behavioural issues and sleep disturbances increased. To our knowledge this is the first case report demonstrating the success of escitalopram in managing behavioural problems associated with Rett syndrome. SSRIs may assist through
different mechanisms. Fluoxetine increases MeCP2 expression in rat brains (Chapleau et al., 2013; Pan and Tsai, 2012). SSRIs have been shown to enhance BDNF expression (Chapleau et al., 2013; Pan and Tsai, 2012). Patients with Rett syndrome and mice null for MeCP2 show reduced levels of brain serotonin, thus by adjusting serotonin levels, SSRIs might improve mood and behavioural disturbance (Chapleau et al., 2013; Percy, 2014). Larger animal and human trials are needed to empirically validate the effectiveness of SSRIs in moderating behavioural and sleep disturbance in Rett syndrome.
Written informed consent from the patient’s parents was obtained prior to submitting this manuscript.
Chapleau CA, Lane J, Pozzo-Miller L, et al. (2013) Evaluation of current pharmacological treatment options in the management of Rett syndrome: from the present to future therapeutic alternatives. Current Clinical Pharmacology 8: 358–369. Pan CH and Tsai S (2012) Early intervention with psychostimulants or antidepressants to increase methyl-CpG-binding protein 2 (MeCP2) expressions: a potential therapy for Rett syndrome. Medical Science Monitor 18: HY1–3. Percy A (2014) Rett syndrome: coming to terms with treatment. Advances in Neuroscience 2014: 345270.
Cyclical suicidal ideation following natalizumab infusion for multiple sclerosis Omkar Nagesh1, Tarun Bastiampillai2, Laura Fisher1 and Titus Mohan1
natalizumab infusion for RRMS worsened depressive symptoms in a cyclical pattern. Ms H is a 51-year-old woman with an 8-year history of depression managed with antidepressants and psychotherapy. Ms H was diagnosed with RRMS in 2012 and despite treatment with fingolimod her neurological symptoms progressively worsened. Therefore, 4-weekly (300 mg IV) natalizumab infusions were commenced. Following natalizumab infusions, Ms H noted a cyclical worsening of her depression associated with intense suicidal ideation. Worsening of symptoms began on day 3 post infusion, reaching maximum intensity on days 5–6, and resolving to baseline by day 10. This pattern was consistently observed
after each natalizumab infusion. Beck Depression Inventory (BDI-II) scores were performed post sixth and seventh natalizumab infusions (Table 1). The rate of depression with natalizumab infusions (19%) was not significant when compared to placebo (McCormack, 2013). However a recent report by Mumoli et al. (2013) suggests a causative link between natalizumab and an attempted suicide. Our patient’s cyclical symptom profile, if observed in others, could inform specific high-risk periods necessitating close monitoring of mental state. In addition to its primary action, natalizumab induces peripheral cellmediated inflammation and secretion of cytokines, particularly TNF-α (McCormack, 2013). An association
1Flinders
Medical Centre, Adelaide, Australia Adelaide, Australia
2SAHMRI,
Corresponding author: Titus Mohan, Flinders Medical Centre, Adelaide, South Australia, 5042, Australia. Email: [email protected] DOI: 10.1177/0004867415572414
To the Editor Immune modulating agents have been associated with depression and suicidality (Mumoli et al., 2013). Natalizumab is a monoclonal antibody that slows the progression of relapsing remitting multiple sclerosis (RRMS). Natalizumab blocks the migration of T cells across the blood brain barrier (BBB) preventing further demyelination and plaque formation (McCormack, 2013). We present an intriguing scenario wherein
Consent
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References
Table 1. Beck Depression Inventory (BDI-II) scores following infusions 6 and 7. Infusion cycle Day post infusion
Sixth
Seventh
0
31
31
5
41
42
10
35
33
15
30
29
Australian & New Zealand Journal of Psychiatry, 49(7) Downloaded from anp.sagepub.com at UNIV TORONTO on November 16, 2015
669
ANZJP Correspondence Declaration of interest
between peripheral inflammation and depression has been reported (Postal and Appenzeller, 2015). While peripheral cytokines do not normally cross the BBB, primary afferent nerves, the choroid plexus and specific transporter proteins facilitate cytokine movement from peripheral inflammatory sites to the central nervous system (CNS) (Postal and Appenzeller, 2014). It is possible that transmission of cytokines and other peripheral inflammatory signals to the CNS could be the basis for worsening depressive symptoms and suicidal ideation following natalizumab infusions.
Quantification of peripheral cytokine levels and temporal correlation with severity of depression/suicidal ideation following natalizumab infusions may provide some theoretical basis for the cyclical symptoms demonstrated by our patient. Such correlation, if it exists, also affirms the increasingly recognised role of the immune system in the pathogenesis of depression.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors
McCormack PL (2013) Natalizumab: A review of its use in the management of relapsing-remitting multiple sclerosis. Drugs 73: 1463–1481. Mumoli L, Ciriaco M, Gambardella A, et al. (2013) A possible case of Natalizumab-dependent suicide attempt: A brief review about drugs and suicide. Journal of Pharmacology and Pharmacotherapeutics 4 (Suppl 1): S90–S93. Postal M and Appenzeller S (2015) The importance of cytokines and autoantibodies in depression. Autoimmunity Reviews 14: 30–35.
Risperidone exacerbates Psychosis: A paradoxical phenomenon? Chih-Chao Hsu1*, Chia-Jung Lin2*, Ti Lu1 and Li-Yu Hu1
dosage in a patient with hydrocephalus-induced psychosis. Following shunt surgery for hydrocephalus caused by a posterior fossa arachanoid cyst, a 22-year-old boy experienced auditory hallucinations and persecutory delusions. He had no history of psychotic symptoms or substance abuse before the surgery. We prescribed risperidone (2 mg per day) for the psychotic symptoms. After initial improvement, the symptoms gradually exacerbated 2 years later. No precipitating factor was confirmed during this period. To account for poor drug adherence, 25 mg of longacting injectable risperidone every 2 weeks was prescribed. However, the symptoms worsened and his father attributed this to “side effects from the antipsychotics, especially the longacting injectable one.” Therefore, acute ward admission was arranged 2 months later. Thorough physical examination including brain imaging and blood sampling revealed no active change. His psychotic symptoms with disorganized behavioral disturbance gradually subsided after reducing oral risperidone to 1 mg per day and discontinuing the injectable risperidone. Risperidone was then discontinued entirely and we prescribed flupentixol (3 mg per day) instead. This resulted in a more stable mental condition
without behavioral disturbance within 45 days after admission. Few studies directly mention that risperidone exacerbates psychotic symptoms in hydrocephalus-induced psychosis. However, D2 receptor over-expression in the striatum could possibly be related to psychotic symptoms and behavioral disturbance (Kellendonk et al., 2006). Striatal dopamine D2 receptors are known to be up-regulated in patients with hydrocephalus post the shunting procedure and on long-term risperidone treatment (Nakayama et al., 2007, Tarazi et al., 2001). In conclusion, the synergistic effects of shunting surgery for hydrocephalus in combination with risperidone treatment could have upregulated the levels of striatal D2 receptors and increased the psychosis. Although clinical confounders such as illicit drug use, poor drug adherence, or an inadequate family support system could influence the patient’s condition, the paradoxical effect of risperidone, which to our knowledge has not been reported previously, might explain the clinical presentation of our case. This effect should be considered when selecting antipsychotics for hydrocephalus in patients with psychotic symptoms, especially for long-term use and at higher doses.
1Department
of Psychiatry, Kaohsiung Veterans General Hospital, Kaoshiung, Taiwan 2Department of Nursing, Yuanshan & Su’ao Branch, Taipei Veterans General Hospital, Yilan, Taiwan *Chih-Chao Hsu and Chia-Jung Lin contributed equally to this manuscript Corresponding author: Li-Yu Hu, No. 386, Ta-Chung 1st Road, TzuoYin District, Kaohsiung City, 81362, Taiwan. Email: [email protected] DOI: 10.1177/0004867415574749
To the Editor Hydrocephalus manifests as abnormal accumulation of cerebrospinal fluid and dilated ventricles. These structural changes can induce psychiatric complications, including psychotic symptoms; therefore, antipsychotics are prescribed. However, treatment for hydrocephalus-induced psychosis has not been well investigated and the present choice of antipsychotics is on a case-by-case basis. This letter reports a case of progressive psychotic symptoms concurrent with increasing risperidone
Funding
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
Australian & New Zealand Journal of Psychiatry, 49(7)
Downloaded from anp.sagepub.com at UNIV TORONTO on November 16, 2015
