Australian and New Zealand Journal of Psychiatry http://anp.sagepub.com/
Teratology: More than malformations Megan Galbally Aust N Z J Psychiatry 2013 47: 1082 DOI: 10.1177/0004867413495931 The online version of this article can be found at: http://anp.sagepub.com/content/47/11/1082
Published by: http://www.sagepublications.com
On behalf of:
The Royal Australian and New Zealand College of Psychiatrists
Additional services and information for Australian and New Zealand Journal of Psychiatry can be found at: Email Alerts: http://anp.sagepub.com/cgi/alerts Subscriptions: http://anp.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> Version of Record - Nov 6, 2013 What is This?
Downloaded from anp.sagepub.com at University of Waikato Library on July 13, 2014
1082
ANZJP Correspondence
may arise as a consequence of being pregnant, with a misattribution of symptoms. Such symptoms may also arise as a consequence of the poor sleep associated with pregnancy. When assessing depressive symptoms in pregnancy, care needs to be taken to ensure the symptoms are not the result of other factors, such as discontinuation syndrome (if antidepressants have been withdrawn), sleep disturbance, or physical complaints associated with the pregnancy. Such symptoms also need to be assessed carefully, and not just cross-sectionally, as some depressive-like symptoms may be transient expressions of distress and do not require treatment. The final issue is the severity of the depression, as many women may be experiencing mild to moderate depression.There is increasing evidence about the low efficacy of SSRIs in mild to moderate depression, with little difference seen between drug and placebo in clinical trials (Barbui et al., 2011). It needs to be emphasised that pregnant women are routinely excluded from clinical trials. Non-pharmacological treatments may be more appropriate for depression in pregnancy. So what should a clinician conclude from these observations? There are two take-home messages. First, while there is a small, but acceptable increased risk of congenital abnormalities following exposure to SSRIs, there are other risks to be taken into account. Given this, I would
argue that caution is still warranted in prescribing antidepressant medication during pregnancy, especially when there are alternative, effective and safe nonpharmacological treatments that can be applied for depression in pregnancy. If there are clear indications that pharmacotherapy is necessary (such as for moderate to severe depression or disabling anxiety), then it should be used ideally at the lowest effective dose. Second, we should always be mindful of the risks associated with antidepressants when prescribing them to any woman of childbearing age. Women should be informed about these risks at the initiation of treatment and their treatment reviewed if they want to conceive. If this is not under consideration, then having a discussion about contraception is important.
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. 5th edn. Arlington,VA: American Psychiatric Publishing.
Barbui C, Cipriani A, Patel V, et al. (2011) Efficacy of antidepressants and benzodiazepines in minor depression: Systematic review and metaanalysis. British Journal of Psychiatry 198: 11–16. Chaudron LH (2013) Complex challenges in treating depression during pregnancy. American Journal of Psychiatry 170: 12–20. Cohen LS, Altshuler LL, Harlow BL, et al. (2006) Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA: The Journal of the American Medical Association 295: 499–507. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. (2013a) The impact of maternal depression during pregnancy on perinatal outcomes: A systematic review and meta-analysis. Journal of Clinical Psychiatry 74: e321–e341. Grigoriadis S, Vonderporten EH, Mamisashvili L, et al. (2013b) The effect of prenatal antidepressant exposure on neonatal adaptation: a systematic review and metaanalysis. Journal of Clinical Psychiatry 74: e309–e320. Jensen HM, Grøn R, Lidegaard Ø, et al. (2013) Maternal depression, antidepressant use in pregnancy and Apgar scores in infants. British Journal Of Psychiatry: The Journal of Mental Science 202: 347–351. Myles N, Newall H, Ward H, et al. (2013) Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations. Australian and New Zealand Journal of Psychiatry. Epub ahead of print 12 June 2013. DOI: 10.1177/0004867413492219. Odd DE, Rasmussen F, Gunnell D, et al. (2008) A cohort study of low Apgar scores and cognitive outcomes. Archives of Disease in Childhood. Fetal and Neonatal Edition 93: F115–F120. Toh S, Mitchell AA, Louik C, et al. (2009) Selective serotonin reuptake inhibitor use and risk of gestational hypertension. American Journal of Psychiatry 166: 320–328.
Teratology: More than malformations Megan Galbally1,2
Myles et al., 2013 is the eighth metaanalysis to examine the question as to whether first trimester exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants is associated with malformations. To date four have found no association (Addis and Koren, 2000; Einarson and Einarson, 2005; O’Brien et al., 2008; Rahimi et al., 2006) and two have found an association between paroxetine and cardiac malformations (Bar-Oz et al., 2007; Wurst et al., 2010). The two most recent, Myles et al., 2013 and Grigoriadis et al.,
2013 have also found a significant association between paroxetine and cardiac malformations and in addition found an association between fluoxetine and malformations. This lack of consistent findings is puzzling for clinicians to interpret and anxiety-provoking for women who are prescribed antidepressants in pregnancy. While rates of antidepressant use in pregnancy are relatively low in Australia, with a recent study showing 2.1% (Lewis et al., 2012), in North America the trend is towards
1Perinatal
Mental Health, Mercy Hospital for Women, Heidelberg, Australia 2Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia Corresponding author: Megan Galbally, Perinatal Mental Health, Mercy Hospital for Women, 163 Studley Rd, Heidelberg, VIC 3084, Australia. Email: [email protected] DOI: 10.1177/0004867413495931
Funding PB has received unrestricted educational grants from Servier and research funding from Eli Lilly.
Declaration of interest PB has been on the advisory boards of Eli Lilly, AstraZeneca and Lundbeck. He has received honoraria for speaking for Servier and AstraZeneca. He has been involved in clinical trials for Janssen-Cilag, The Brain Resource Company and Servier.
References
Australian & New Zealand Journal of Psychiatry, 47(11) Downloaded from anp.sagepub.com at University of Waikato Library on July 13, 2014
1083
ANZJP Correspondence increasing antidepressant usage in pregnancy, with rates documented between 5% and 13%. These rising rates of exposure to antidepressants in pregnancy have mirrored the substantial increase in publications and studies on the risks of exposure. However, many of these newer publications are based either on retrospective reviews of medical records or on retrospective studies of population registers, which frequently were not designed for research purposes. This has led to a number of studies having major limitations with crucial concerns such as accuracy of data on exposure, including timing and lack of adequate measures of maternal mental illness, and key confounding variables. While Myles et al., 2013 and Grigoriadis et al., 2013 have both included all methodologies in their meta-analyses, earlier reviews have selected only prospective cohort studies. Interestingly, those that have selected only prospective studies have not found an association between malformations and antidepressants (Einarson and Einarson, 2005). This is one of the reasons there has been a consistent call for more prospective studies which include careful measures of exposure, maternal mental illness and confounding variables. Given the general risk for malformations is between 2% and 3% and the principles of teratology require a specific malformation to be associated with a specific exposure, with commonly a dosage effect, untangling what may be caused by antidepressant exposure, what may be associated with other associated confounding variables and what may be explained by baseline population rates is challenging. For instance, several studies have now found the use of antidepressants in pregnancy is also associated with higher smoking and alcohol intake. In one study of malformations and antidepressant use the rate of fetal alcohol syndrome in SSRIexposed neonates was 10 times higher than the control group (Malm et al.,
2011). In studies of pregnant women taking antidepressant treatment there is yet to be an examination of other key variables associated with elevated malformation rates, such as obesity and nutritional status including prenatal folate use. In addition, maternal illnesses, such as diabetes, are defined also as teratogens, and it warrants further studies to clarify if maternal mental illnesses, particularly anxiety, are also potentially implicated. Given paroxetine is frequently prescribed for anxiety disorders and the evidence for adverse pregnancy outcomes and mental illness has been focused on anxiety in pregnancy, this clearly requires further exploration. With so many questions still to be answered there is an urgent need for welldesigned, prospective studies that are adequately powered to untangle the complexity of exposures and outcomes for women and infants. However, beyond the concern of structural teratology is the relatively unexplored territory of neurodevelopmental teratology. A systematic review in 2010 identified only 12 studies that have examined neurodevelopmental outcomes for children following antidepressant exposure; only half of these studies examined children aged 12 months or older and none at school age or beyond (Gentile and Galbally, 2010). The identified studies were methodologically heterogeneous with few using neuropsychological measures with predictive validity for effects on later child development. This contrasts with the anti-epileptic drugs where there are a number of highquality prospective studies using comprehensive neuropsychological tests (Galbally et al., 2010). However, despite the limited spectrum of studies for antidepressant exposure and neurodevelopmental outcomes, there have now been four studies that have identified poorer motor development in children exposed to antidepressants in utero, including our own (Galbally et al., 2011). This clearly warrants further investigation with larger, prospective longitudinal studies with
comprehensive neuropsychological assessment of children at an age and with measures that can accurately determine if this is a ‘real’ finding. Systematic reviews and metaanalysis are useful in identifying potential risks, particularly for rare conditions or where studies available are mostly small and inconclusive. However, the current state of research into antidepressant exposure in pregnancy often results in meta-analysis leading to more questions than answers. There now needs to be a concerted effort to fill the knowledge gaps with purpose-designed, longitudinal, prospective studies which include measures of maternal illness, accurate records of exposure and a range of key confounding variables. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. See Review by Myles et al., 2013, 47(11): 1002–1012.
References Addis A and Koren G (2000) Safety of fluoxetine during the first trimester of pregnancy: A meta-analytical review of epidemiological studies. Psychological Medicine 30: 89–94. Bar-Oz B, Einarson T, Einarson A, et al. (2007) Paroxetine and congenital malformations: Meta-analysis and consideration of potential confounding factors. Clinical Therapeutics 29: 918–926. Einarson TR and Einarson A (2005) Newer antidepressants in pregnancy and rates of major malformations: A meta-analysis of prospective comparative studies. Pharmacoepidemiology and Drug Safety 14: 823–827. Galbally M, Roberts M and Buist A (2010) Mood stabilizers in pregnancy: A systematic review. Australian and New Zealand Journal of Psychiatry 44: 967–977. Galbally M, Lewis, AJ and Buist A (2011) Developmental outcomes of children exposed to antidepressants in pregnancy. Australian and New Zealand Journal of Psychiatry 45: 393–399.
Australian & New Zealand Journal of Psychiatry, 47(11)
Downloaded from anp.sagepub.com at University of Waikato Library on July 13, 2014
1084
ANZJP Correspondence
Gentile S and Galbally M (2010) Prenatal exposure to antidepressant medications and neuro-developmental outcomes: A systematic review. Journal of Affective Disorders 128: 1–9. Grigoriadis S, Vonderporten EH, Mamisashvili L, et al. (2013) Antidepressant exposure during pregnancy and congenital malformations: is there an association? a systematic review and meta-analysis of the best evidence. Journal of Clinical Psychiatry 74: e293–e308. Lewis A, Galbally M and Bailey C (2012) Perinatal mental health, antidepressants and neonatal outcomes: Findings from the Longitudinal
Study of Australian Children. Neonatal, Paediatric and Child Health Nursing 15: 22–28. Malm H, Artama M, Gissler M, et al. (2011) Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstetrics & Gynecology 118: 111–120. Myles N, Newall H, Ward H and Large M (2013) Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations. Australian and New Zealand Journal of Psychiatry 47: 1001–1011. O’Brien L, Einarson TR, Sarkar M, et al. (2008) Does paroxetine cause cardiac malformations?
Journal of Obstetrics and Gynaecology Canada 30: 696–701. Rahimi R, Nikfar S and Abdollahi M (2006) Pregnancy outcomes following exposure to serotonin reuptake inhibitors: A meta-analysis of clinical trials. Reproductive Toxicology 22: 571–575. Wurst KE, Poole C, Ephross SA, et al. (2010) First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: A meta-analysis of epidemiological studies. Birth Defects Research. Part A, Clinical and Molecular Teratology 88: 159–170.
Use of quetiapine in child and adolescent populations – Response to letter from Dr Lambe Erik Monasterio and Andrew McKean
encourage close attention to recent findings in the literature, which indicate that there has been a particularly rapid expansion in the use of these agents in this age group for reasons which remain largely unknown.
from 1993/1995 to 2002 (Olfson et al., 2006). Amongst privately insured 2–5-year-old children in the USA, the rate of antipsychotic use doubled in the period of 1999/2001 to 2007; this occurred at the same time that the use of antidepressants decreased (1.6 times less common in 2007) in this age group (Olfson et al., 2010). Data from long-term US trends in office-based physician use of antipsychotic medications found that there was an eightfold increase in the number of treatment visits for children between 1995 and 2008 (Alexander et al., 2011). In British Columbia, there has been a 10-fold increase in the prescription of AAPs to children under 14 between 1997 and 2007 (Panagiotopoulos et al., 2010). •• Data supplied by PHARMAC (the pharmaceutical funding agency in New Zealand) indicates that there has been a 56% increase in the use of antipsychotic medications in 10–19 year olds from 2008 to 2012 in New Zealand. •• Children and adolescents may be at a higher risk of antipsychoticassociated weight gain, as well as sedation and movement disorders, when compared to adults (McKinney and Renk, 2011). Among 257 children taking second-generation antipsychotics for the first time, weight increased during the first 12 weeks of treatment. Among subjects taking olanzapine, the mean weight gain was
Hillmorton Hospital, Christchurch, New Zealand Corresponding author: Erik Monasterio, Hillmorton Hospital, Annex Road, Christchurch 8140, New Zealand. Email: [email protected] DOI: 10.1177/0004867413498274
We are grateful to be given an opportunity to comment on the letter by Dr Lambe (Lambe, 2013) in response to our previous correspondence (Monasterio and McKean, 2013), which outlined our concern about the extensive off-label use of quetiapine in primary and specialist psychiatric care, despite the limited evidence base for its safety and efficacy (Monasterio and McKean, 2011). Dr Lambe acknowledges that there are many potential adverse effects associated with the use of quetiapine, particularly in child and adolescent psychiatry, but, despite this, comments that: ‘off-label prescribing of quetiapine for excessive anxiety and insomnia is often the best alternative, as long as one monitors for side effects’ (Lambe, 2013). In considering the appropriateness of off-label prescribing of atypical antipsychotic (AAP) medications in child and adolescent psychiatry, we
•• An analysis of drug dispensing data from community pharmacies in The Netherlands found that between 1997 and 2005 the use of antipsychotics increased from 3.0 to 6.8 per thousand for youths to 19 years of age; the use of AAPs increased almost ninefold. The increase in AAPs was most pronounced for 5–9 year olds (almost 10-fold) and for 10–14 year olds (almost 12-fold). The median duration of AAP use across all age groups was 2.9 years and longest for 5-9 year olds, at 5.1 years. (Kalverdijk et al., 2008). •• An analysis of Medical Expen ditures Panel Survey (MEPS) data on non-institutionalized individuals in the USA found that the proportion of antipsychotic users who were under age 18 doubled between 1996/1997 and 2004/ 2005 from 7% to 15% of all users (Domino and Swartz, 2008). Analysis of data from the National Ambulatory Medical Care Survey (NAMCS), which collects information from office-based physician practices, found that the annual number of US office visits by those under age 21 that included prescription of an antipsychotic medication jumped more than fivefold
Australian & New Zealand Journal of Psychiatry, 47(11) Downloaded from anp.sagepub.com at University of Waikato Library on July 13, 2014
Teratology: More than malformations Megan Galbally Aust N Z J Psychiatry 2013 47: 1082 DOI: 10.1177/0004867413495931 The online version of this article can be found at: http://anp.sagepub.com/content/47/11/1082
Published by: http://www.sagepublications.com
On behalf of:
The Royal Australian and New Zealand College of Psychiatrists
Additional services and information for Australian and New Zealand Journal of Psychiatry can be found at: Email Alerts: http://anp.sagepub.com/cgi/alerts Subscriptions: http://anp.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> Version of Record - Nov 6, 2013 What is This?
Downloaded from anp.sagepub.com at University of Waikato Library on July 13, 2014
1082
ANZJP Correspondence
may arise as a consequence of being pregnant, with a misattribution of symptoms. Such symptoms may also arise as a consequence of the poor sleep associated with pregnancy. When assessing depressive symptoms in pregnancy, care needs to be taken to ensure the symptoms are not the result of other factors, such as discontinuation syndrome (if antidepressants have been withdrawn), sleep disturbance, or physical complaints associated with the pregnancy. Such symptoms also need to be assessed carefully, and not just cross-sectionally, as some depressive-like symptoms may be transient expressions of distress and do not require treatment. The final issue is the severity of the depression, as many women may be experiencing mild to moderate depression.There is increasing evidence about the low efficacy of SSRIs in mild to moderate depression, with little difference seen between drug and placebo in clinical trials (Barbui et al., 2011). It needs to be emphasised that pregnant women are routinely excluded from clinical trials. Non-pharmacological treatments may be more appropriate for depression in pregnancy. So what should a clinician conclude from these observations? There are two take-home messages. First, while there is a small, but acceptable increased risk of congenital abnormalities following exposure to SSRIs, there are other risks to be taken into account. Given this, I would
argue that caution is still warranted in prescribing antidepressant medication during pregnancy, especially when there are alternative, effective and safe nonpharmacological treatments that can be applied for depression in pregnancy. If there are clear indications that pharmacotherapy is necessary (such as for moderate to severe depression or disabling anxiety), then it should be used ideally at the lowest effective dose. Second, we should always be mindful of the risks associated with antidepressants when prescribing them to any woman of childbearing age. Women should be informed about these risks at the initiation of treatment and their treatment reviewed if they want to conceive. If this is not under consideration, then having a discussion about contraception is important.
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. 5th edn. Arlington,VA: American Psychiatric Publishing.
Barbui C, Cipriani A, Patel V, et al. (2011) Efficacy of antidepressants and benzodiazepines in minor depression: Systematic review and metaanalysis. British Journal of Psychiatry 198: 11–16. Chaudron LH (2013) Complex challenges in treating depression during pregnancy. American Journal of Psychiatry 170: 12–20. Cohen LS, Altshuler LL, Harlow BL, et al. (2006) Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA: The Journal of the American Medical Association 295: 499–507. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. (2013a) The impact of maternal depression during pregnancy on perinatal outcomes: A systematic review and meta-analysis. Journal of Clinical Psychiatry 74: e321–e341. Grigoriadis S, Vonderporten EH, Mamisashvili L, et al. (2013b) The effect of prenatal antidepressant exposure on neonatal adaptation: a systematic review and metaanalysis. Journal of Clinical Psychiatry 74: e309–e320. Jensen HM, Grøn R, Lidegaard Ø, et al. (2013) Maternal depression, antidepressant use in pregnancy and Apgar scores in infants. British Journal Of Psychiatry: The Journal of Mental Science 202: 347–351. Myles N, Newall H, Ward H, et al. (2013) Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations. Australian and New Zealand Journal of Psychiatry. Epub ahead of print 12 June 2013. DOI: 10.1177/0004867413492219. Odd DE, Rasmussen F, Gunnell D, et al. (2008) A cohort study of low Apgar scores and cognitive outcomes. Archives of Disease in Childhood. Fetal and Neonatal Edition 93: F115–F120. Toh S, Mitchell AA, Louik C, et al. (2009) Selective serotonin reuptake inhibitor use and risk of gestational hypertension. American Journal of Psychiatry 166: 320–328.
Teratology: More than malformations Megan Galbally1,2
Myles et al., 2013 is the eighth metaanalysis to examine the question as to whether first trimester exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants is associated with malformations. To date four have found no association (Addis and Koren, 2000; Einarson and Einarson, 2005; O’Brien et al., 2008; Rahimi et al., 2006) and two have found an association between paroxetine and cardiac malformations (Bar-Oz et al., 2007; Wurst et al., 2010). The two most recent, Myles et al., 2013 and Grigoriadis et al.,
2013 have also found a significant association between paroxetine and cardiac malformations and in addition found an association between fluoxetine and malformations. This lack of consistent findings is puzzling for clinicians to interpret and anxiety-provoking for women who are prescribed antidepressants in pregnancy. While rates of antidepressant use in pregnancy are relatively low in Australia, with a recent study showing 2.1% (Lewis et al., 2012), in North America the trend is towards
1Perinatal
Mental Health, Mercy Hospital for Women, Heidelberg, Australia 2Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia Corresponding author: Megan Galbally, Perinatal Mental Health, Mercy Hospital for Women, 163 Studley Rd, Heidelberg, VIC 3084, Australia. Email: [email protected] DOI: 10.1177/0004867413495931
Funding PB has received unrestricted educational grants from Servier and research funding from Eli Lilly.
Declaration of interest PB has been on the advisory boards of Eli Lilly, AstraZeneca and Lundbeck. He has received honoraria for speaking for Servier and AstraZeneca. He has been involved in clinical trials for Janssen-Cilag, The Brain Resource Company and Servier.
References
Australian & New Zealand Journal of Psychiatry, 47(11) Downloaded from anp.sagepub.com at University of Waikato Library on July 13, 2014
1083
ANZJP Correspondence increasing antidepressant usage in pregnancy, with rates documented between 5% and 13%. These rising rates of exposure to antidepressants in pregnancy have mirrored the substantial increase in publications and studies on the risks of exposure. However, many of these newer publications are based either on retrospective reviews of medical records or on retrospective studies of population registers, which frequently were not designed for research purposes. This has led to a number of studies having major limitations with crucial concerns such as accuracy of data on exposure, including timing and lack of adequate measures of maternal mental illness, and key confounding variables. While Myles et al., 2013 and Grigoriadis et al., 2013 have both included all methodologies in their meta-analyses, earlier reviews have selected only prospective cohort studies. Interestingly, those that have selected only prospective studies have not found an association between malformations and antidepressants (Einarson and Einarson, 2005). This is one of the reasons there has been a consistent call for more prospective studies which include careful measures of exposure, maternal mental illness and confounding variables. Given the general risk for malformations is between 2% and 3% and the principles of teratology require a specific malformation to be associated with a specific exposure, with commonly a dosage effect, untangling what may be caused by antidepressant exposure, what may be associated with other associated confounding variables and what may be explained by baseline population rates is challenging. For instance, several studies have now found the use of antidepressants in pregnancy is also associated with higher smoking and alcohol intake. In one study of malformations and antidepressant use the rate of fetal alcohol syndrome in SSRIexposed neonates was 10 times higher than the control group (Malm et al.,
2011). In studies of pregnant women taking antidepressant treatment there is yet to be an examination of other key variables associated with elevated malformation rates, such as obesity and nutritional status including prenatal folate use. In addition, maternal illnesses, such as diabetes, are defined also as teratogens, and it warrants further studies to clarify if maternal mental illnesses, particularly anxiety, are also potentially implicated. Given paroxetine is frequently prescribed for anxiety disorders and the evidence for adverse pregnancy outcomes and mental illness has been focused on anxiety in pregnancy, this clearly requires further exploration. With so many questions still to be answered there is an urgent need for welldesigned, prospective studies that are adequately powered to untangle the complexity of exposures and outcomes for women and infants. However, beyond the concern of structural teratology is the relatively unexplored territory of neurodevelopmental teratology. A systematic review in 2010 identified only 12 studies that have examined neurodevelopmental outcomes for children following antidepressant exposure; only half of these studies examined children aged 12 months or older and none at school age or beyond (Gentile and Galbally, 2010). The identified studies were methodologically heterogeneous with few using neuropsychological measures with predictive validity for effects on later child development. This contrasts with the anti-epileptic drugs where there are a number of highquality prospective studies using comprehensive neuropsychological tests (Galbally et al., 2010). However, despite the limited spectrum of studies for antidepressant exposure and neurodevelopmental outcomes, there have now been four studies that have identified poorer motor development in children exposed to antidepressants in utero, including our own (Galbally et al., 2011). This clearly warrants further investigation with larger, prospective longitudinal studies with
comprehensive neuropsychological assessment of children at an age and with measures that can accurately determine if this is a ‘real’ finding. Systematic reviews and metaanalysis are useful in identifying potential risks, particularly for rare conditions or where studies available are mostly small and inconclusive. However, the current state of research into antidepressant exposure in pregnancy often results in meta-analysis leading to more questions than answers. There now needs to be a concerted effort to fill the knowledge gaps with purpose-designed, longitudinal, prospective studies which include measures of maternal illness, accurate records of exposure and a range of key confounding variables. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. See Review by Myles et al., 2013, 47(11): 1002–1012.
References Addis A and Koren G (2000) Safety of fluoxetine during the first trimester of pregnancy: A meta-analytical review of epidemiological studies. Psychological Medicine 30: 89–94. Bar-Oz B, Einarson T, Einarson A, et al. (2007) Paroxetine and congenital malformations: Meta-analysis and consideration of potential confounding factors. Clinical Therapeutics 29: 918–926. Einarson TR and Einarson A (2005) Newer antidepressants in pregnancy and rates of major malformations: A meta-analysis of prospective comparative studies. Pharmacoepidemiology and Drug Safety 14: 823–827. Galbally M, Roberts M and Buist A (2010) Mood stabilizers in pregnancy: A systematic review. Australian and New Zealand Journal of Psychiatry 44: 967–977. Galbally M, Lewis, AJ and Buist A (2011) Developmental outcomes of children exposed to antidepressants in pregnancy. Australian and New Zealand Journal of Psychiatry 45: 393–399.
Australian & New Zealand Journal of Psychiatry, 47(11)
Downloaded from anp.sagepub.com at University of Waikato Library on July 13, 2014
1084
ANZJP Correspondence
Gentile S and Galbally M (2010) Prenatal exposure to antidepressant medications and neuro-developmental outcomes: A systematic review. Journal of Affective Disorders 128: 1–9. Grigoriadis S, Vonderporten EH, Mamisashvili L, et al. (2013) Antidepressant exposure during pregnancy and congenital malformations: is there an association? a systematic review and meta-analysis of the best evidence. Journal of Clinical Psychiatry 74: e293–e308. Lewis A, Galbally M and Bailey C (2012) Perinatal mental health, antidepressants and neonatal outcomes: Findings from the Longitudinal
Study of Australian Children. Neonatal, Paediatric and Child Health Nursing 15: 22–28. Malm H, Artama M, Gissler M, et al. (2011) Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstetrics & Gynecology 118: 111–120. Myles N, Newall H, Ward H and Large M (2013) Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations. Australian and New Zealand Journal of Psychiatry 47: 1001–1011. O’Brien L, Einarson TR, Sarkar M, et al. (2008) Does paroxetine cause cardiac malformations?
Journal of Obstetrics and Gynaecology Canada 30: 696–701. Rahimi R, Nikfar S and Abdollahi M (2006) Pregnancy outcomes following exposure to serotonin reuptake inhibitors: A meta-analysis of clinical trials. Reproductive Toxicology 22: 571–575. Wurst KE, Poole C, Ephross SA, et al. (2010) First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: A meta-analysis of epidemiological studies. Birth Defects Research. Part A, Clinical and Molecular Teratology 88: 159–170.
Use of quetiapine in child and adolescent populations – Response to letter from Dr Lambe Erik Monasterio and Andrew McKean
encourage close attention to recent findings in the literature, which indicate that there has been a particularly rapid expansion in the use of these agents in this age group for reasons which remain largely unknown.
from 1993/1995 to 2002 (Olfson et al., 2006). Amongst privately insured 2–5-year-old children in the USA, the rate of antipsychotic use doubled in the period of 1999/2001 to 2007; this occurred at the same time that the use of antidepressants decreased (1.6 times less common in 2007) in this age group (Olfson et al., 2010). Data from long-term US trends in office-based physician use of antipsychotic medications found that there was an eightfold increase in the number of treatment visits for children between 1995 and 2008 (Alexander et al., 2011). In British Columbia, there has been a 10-fold increase in the prescription of AAPs to children under 14 between 1997 and 2007 (Panagiotopoulos et al., 2010). •• Data supplied by PHARMAC (the pharmaceutical funding agency in New Zealand) indicates that there has been a 56% increase in the use of antipsychotic medications in 10–19 year olds from 2008 to 2012 in New Zealand. •• Children and adolescents may be at a higher risk of antipsychoticassociated weight gain, as well as sedation and movement disorders, when compared to adults (McKinney and Renk, 2011). Among 257 children taking second-generation antipsychotics for the first time, weight increased during the first 12 weeks of treatment. Among subjects taking olanzapine, the mean weight gain was
Hillmorton Hospital, Christchurch, New Zealand Corresponding author: Erik Monasterio, Hillmorton Hospital, Annex Road, Christchurch 8140, New Zealand. Email: [email protected] DOI: 10.1177/0004867413498274
We are grateful to be given an opportunity to comment on the letter by Dr Lambe (Lambe, 2013) in response to our previous correspondence (Monasterio and McKean, 2013), which outlined our concern about the extensive off-label use of quetiapine in primary and specialist psychiatric care, despite the limited evidence base for its safety and efficacy (Monasterio and McKean, 2011). Dr Lambe acknowledges that there are many potential adverse effects associated with the use of quetiapine, particularly in child and adolescent psychiatry, but, despite this, comments that: ‘off-label prescribing of quetiapine for excessive anxiety and insomnia is often the best alternative, as long as one monitors for side effects’ (Lambe, 2013). In considering the appropriateness of off-label prescribing of atypical antipsychotic (AAP) medications in child and adolescent psychiatry, we
•• An analysis of drug dispensing data from community pharmacies in The Netherlands found that between 1997 and 2005 the use of antipsychotics increased from 3.0 to 6.8 per thousand for youths to 19 years of age; the use of AAPs increased almost ninefold. The increase in AAPs was most pronounced for 5–9 year olds (almost 10-fold) and for 10–14 year olds (almost 12-fold). The median duration of AAP use across all age groups was 2.9 years and longest for 5-9 year olds, at 5.1 years. (Kalverdijk et al., 2008). •• An analysis of Medical Expen ditures Panel Survey (MEPS) data on non-institutionalized individuals in the USA found that the proportion of antipsychotic users who were under age 18 doubled between 1996/1997 and 2004/ 2005 from 7% to 15% of all users (Domino and Swartz, 2008). Analysis of data from the National Ambulatory Medical Care Survey (NAMCS), which collects information from office-based physician practices, found that the annual number of US office visits by those under age 21 that included prescription of an antipsychotic medication jumped more than fivefold
Australian & New Zealand Journal of Psychiatry, 47(11) Downloaded from anp.sagepub.com at University of Waikato Library on July 13, 2014
