- Email: [email protected]
Effectiveness of ropinirole for RLS and depressive symptoms in an 11-year-old girl
Sleep Medicine 10 (2009) 259–261 www.elsevier.com/locate/sleep
Case Report
Effectiveness of ropinirole for RLS and depressive symptoms in an 11-year-old girl Samuele Cortese a,b,*, Eric Konofal a,c,d, Michel Lecendreux a,c b
a APHP, Child and Adolescent Psychopathology Unit, Robert Debre´ Hospital, Paris VII University, Paris, France Child Neuropsychiatry Unit, G.B. Rossi Hospital, Department of Mother-Child and Biology-Genetics, Verona University, Verona, Italy c APHP, Pediatric Sleep Disorders Center, Robert Debre´ Hospital, Paris, France d APHP, Sleep Disorders Center, Pitie´-Salpeˆtrie`re Hospital, Paris, France
Received 8 August 2007; received in revised form 16 October 2007; accepted 18 October 2007 Available online 4 March 2008
Abstract An 11-year-old girl was referred for an irresistible urge to move her legs associated with uncomfortable sensations. She was diagnosed with definite Restless Legs Syndrome (RLS) according to 2003 NIH criteria. The IRLSSG severity scale score was 31 (very severe). The girl also presented with dysthymic disorder according to DSM-IV criteria, as confirmed by the semi-structured interview Kiddie-SADS-PL. The score on the Children Depression Inventory (CDI) was in the clinical range (21). The total score on the Sleep Disturbance Scale for Children (SDSC) was 100. A standard PSG revealed a periodic limb movement index of 16.5, indicating that the child also presented with Periodic Limb Movements Disorder. The girl was treated with ropinirole (a D2/D3 dopamine agonist). After 3 months of treatment (0.50 mg/day at 8.00 PM), RLS, as well as depressive symptoms, remarkably improved, as suggested by the improvement in the IRLSSG severity and CDI scores (14 and 4, respectively). No side effects were reported. The total score on the SDSC also improved (73). The PLM index did not remarkably change. We strongly recommend double blind, randomized, controlled studies to gain insight into the effective treatment strategies for RLS and depression when they coexist in children. Ó 2007 Elsevier B.V. All rights reserved. Keywords: RLS; PLMS; Depression; Ropinirole; Iron; Childhood
1. Introduction Although Restless Legs Syndrome (RLS) has been traditionally considered a disorder of middle to older age, it may occur in children [1]. In 2003, the International Restless Legs Syndrome Study Group (IRLSSG) proposed a set of criteria specific for children [1]. In the first population-based study using these criteria, Picchietti et al. recently found that 1.9% of 8- to 11-year-olds
* Corresponding author. Address: Service de Psychopathologie, de l’Enfant et de l’Adolescent, Hoˆpital Robert Debre´, 48 Boulevard Se´rurier, 75019 Paris, France. Tel.: +33 140032263; fax: +33 140032297. E-mail addresses: [email protected], [email protected] (S. Cortese).
1389-9457/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2007.10.023
and 2.0% of 12- to 17-year-olds presented with definite RLS [2]. At present, evidence on the pharmacological management of RLS in childhood is limited. Case reports have documented the effectiveness of levodopa/carbidopa [3], pergolide [3], ropinirole [4], and pramipexole [5]. Recent evidence from adult studies suggests an interesting but still poorly understood association between RLS and depressive symptoms [6]. To date, this relationship has been scarcely investigated in childhood. So far no evidence-based guidelines are available for the treatment of patients (adults and children) with both RLS and depressive disorders. To gain insight into possible strategies for the management of RLS and depression in childhood, we report
260
S. Cortese et al. / Sleep Medicine 10 (2009) 259–261
the effectiveness of ropinirole (a D2/D3 dopamine agonist) for both RLS and depressive symptoms in an 11year-old girl.
Table 1 Overnight polysomnographic findings before and after 3 months of treatment (ropinirole 0.50 mg/day)
2. Case
TSP (min) TST (min) SE (% of TST) SOL (min) REM onset latency (min) SWS (%TST) REM (%TST) Respiratory index PLM index (/h TST) PLMa index (/h TST) Mean SpO2 (%) SpO2 nadir (%)
The girl was referred to our unit at the age of 11 for an irresistible urge to move her legs associated with uncomfortable sensations, developed after heart surgery at the age of 9 years. The medical history of the child previous to the surgical intervention was normal. No drugs were prescribed to the child previous to the surgical intervention. At the age of 9, the child was diagnosed with an interatrial communication which required surgery. About five days after surgery, the child began to complain of bilaterally uncomfortable sensations in her legs, associated with an urge to move her legs in order to alleviate these sensations. The sensations persisted every day after surgery. The symptomatology was completely absent before the intervention. The child’s mother met RLS criteria. The grandmother complained of similar sensations, but, unfortunately, no other data could be obtained on the grandmother. The father of the patient, her brother, and her sister presented no RLS symptoms. When the patient consulted our Unit, her symptomatology was impairing. She was free from drugs known to cause RLS [1]. The neurological examination was normal. Her Tanner stage was T3. The child met IRLSSG criteria for the diagnosis of definite RLS in children [1]. The IRLSSG severity scale [7] score was 31 (very severe). The T-scores on the Sleep Disturbance Scale for Children (SDSC) [8] were as follows: difficulty in initiating and maintaining sleep (DIMS): 100; sleep breathing disorders (SBD): 45; arousal disorders (DA): 58; sleep– wake transition disorders (SWTD): 91; disorders of excessive somnolence (DOES): 77; sleep hyperhydrosis (SHY): 63; total score (TOT): 100. During the first consultation, the parents reported a dysthymic mood in the patient from almost 18 months. The semi-structured interview Kiddie-SADSPL [9] confirmed the diagnosis of dysthymic disorder according to DSM-IV criteria. The score on the Children Depression Inventory (CDI) [10] (a self-reported questionnaire assessing depressive symptoms in childhood) was 21 (the cut-off for identifying symptoms in the clinical range is 19). No suicidal ideation was reported. Serum ferritin, measured one week after the first consultation, was 19 ng/mL (normal reference range: 15– 40 ng/mL). Haemoglobin level was in the normal range (12.5 g/dL). A standard overnight multichannel PSG was performed one week after the first consultation (Table 1). The periodic limb movements index was 16.5, indicating
Before
After
508 457 89.8 6.0 100.0 29.1 15.7 0.0 16.5 5.4 97.8 95.0
481 411 85.4 6.0 240.0 39.4 14.3 1.0 13.7 5.8 99.0 93.0
TSP, total sleep period; TST, total sleep time; SE, sleep efficiency; SOL, sleep onset latency; SWS, slow wave sleep; REM, rapid eyes movements; PLM, periodic limb movements; PLMa, periodic limb movements with arousals.
that the child also presented with Periodic Limb Movements Disorder (PLMD). After discussing common sleep hygiene rules, we first proposed iron supplementation (ferrous sulphate, 80 mg/day of iron element). After two months, the girl reported only a mild improvement of RLS symptoms (IRLSSG severity scale: 27). No remarkable changes in her mood were found (CDI score: 20). She did not want to engage in psychotherapy. Therefore, after obtaining the parents’ and patient’s agreement, ropinirole was started (0.25 mg/day at 8 p.m.). We did not consider an antidepressant as the first pharmacological option since RLS symptomatology seemed much more impairing than depressive symptoms. Iron supplementation was continued since serum ferritin levels were not remarkably increased (26 ng/mL). After 1 month, a moderate improvement in RLS and depressive symptoms was reported. IRLSSG severity score was 22. CDI score decreased to 18. Ropinirole was well tolerated, with no side effects reported. Serum ferritin levels slightly increased (31 ng/mL). Ropinirole was increased to 0.50 mg/day at 8 p.m. After three months, RLS, as well as depressive symptoms, remarkably improved: IRLSSG severity and CDI scores were 14 and 4, respectively. The T-scores on the SDSC were as follows: DIMS: 82; SBD: 45; DA: 70; SWTD: 58; DOES: 69; SHY: 51; TOT: 73. Serum ferritin levels were 44 ng/mL. The findings on a second PSG are reported in Table 1. The PSG variables did not remarkably change. However, a reduction of periodic limb movements in SWS was found, contributing, in part, to the increase of SWS total time. No side effects were reported by the girl nor by her parents. Vital signs (blood pressure, pulse, and temperature), monitored weekly in the first month and monthly thereafter, were normal.
S. Cortese et al. / Sleep Medicine 10 (2009) 259–261
3. Discussion This is the first case showing the effectiveness and good tolerability of ropinirole for both RLS and depressive symptoms in a young girl. Since RLS preceded depressive mood, which improved after the treatment of RLS, it is possible that RLS contributed to the patient’s depression through its adverse effects on sleep and daytime alertness. Interestingly, the scores on the SDSC in our patient decreased after six months of treatment. It is unlikely that sleep disruption caused by periodic limb movements contributed to depression in our patient since the PLMS index and the PLMS associated with arousals index did not change significantly during treatment. Since periodicity of limb movements is not a consistent finding in childhood [11], we suggest that future studies should investigate the effect of dopaminergic agents on aperiodic limb movements. Another hypothesis explaining how RLS led to depression in our patient is that RLS, like other chronic conditions, induces pain and stress, which, in turn, leads to depressive symptoms associated with low self-esteem. Since depressive symptoms were not present before surgery, we can not rule out the hypothesis that the mood disorder was in part reactive to the past heart surgery. However, since mood improved after the treatment of RLS, we speculate that RLS at least contributed to depressive symptoms. It is also possible that RLS and depression shared common pathophysiological patterns, which may have been the target of the medication. Interestingly, REM latency increased during treatment. Indeed, it is possible that ropinirole increased REM latency, as found in a previous report in adults [12]. The increase of REM latency could be related to the improvement of depressive symptoms, since a reduced REM latency has been reported in childhood depression, paralleling the findings in adults [13]. Independently from the explication of the improvement of RLS and mood, our case suggests that the successful treatment of both RLS and depressive symptoms may be obtained using only RLS treatment. This is of relevance since the common medications used to treat depression (i.e., SSRIs) may aggravate RLS, although recent evidence does not support this statement [14]. We strongly recommend double blind, randomized, controlled studies to gain insight into the effective treat-
261
ment strategies for RLS and depression when they coexist in children.
References [1] Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101–19. [2] Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L. Restless legs syndrome: prevalence and impact in children and adolescents-the Peds REST study. Pediatrics 2007;120:253–66. [3] Walters AS, Mandelbaum DE, Lewin DS, Kugler S, England SJ, Miller M. Dopaminergic therapy in children with restless legs/ periodic limb movements in sleep and ADHD dopaminergic therapy study group. Pediatr Neurol 2000;22:182–6. [4] Konofal E, Arnulf I, Lecendreux M, Mouren MC. Ropinirole in a child with attention-deficit hyperactivity disorder and restless legs syndrome. Pediatr Neurol 2005;32:350–1. [5] Guilleminault C, Palombini L, Pelayo R, Chervin RD. Sleepwalking and sleep terrors in prepubertal children: what triggers them? Pediatrics 2003;111:e17–25. [6] Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep 2005;28:891–8. [7] Hening A, Walters AS, Rosen R. The international RLS study group rating scale: a reliable and valid instrument for assessing severity of the restless legs syndrome. Neurology Suppl 2001;56:A4. [8] Bruni O, Ottaviano S, Guidetti V, Romoli M, Innocenzi M, Cortesi F, et al. The sleep disturbance scale for children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence. J Sleep Res 1996;5:251–61. [9] Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997;36:980–8. [10] Kovacs M. The children’s depression, inventory (CDI). Psychopharmacol Bull 1985;21:995–8. [11] Pennestri MH, Whittom S, Adam B, Petit D, Carrier J, Montplaisir J. PLMS and PLMW in healthy subjects as a function of age: prevalence and interval distribution. Sleep 2006;29:1183–7. [12] Saletu M, Anderer P, Saletu B, Hauer C, Mandl M, Semler B, et al. Sleep laboratory studies in periodic limb movement disorder (PLMD) patients as compared with normals and acute effects of ropinirole. Hum Psychopharmacol 2001;16:177–87. [13] Ivanenko A, Crabtree VM, Gozal D. Sleep and depression in children and adolescents. Sleep Med Rev 2005;9:115–29. [14] Brown LK, Dedrick DL, Doggett JW, Guido PS. Antidepressant medication use and restless legs syndrome in patients presenting with insomnia. Sleep Med 2005;6:443–50.
Case Report
Effectiveness of ropinirole for RLS and depressive symptoms in an 11-year-old girl Samuele Cortese a,b,*, Eric Konofal a,c,d, Michel Lecendreux a,c b
a APHP, Child and Adolescent Psychopathology Unit, Robert Debre´ Hospital, Paris VII University, Paris, France Child Neuropsychiatry Unit, G.B. Rossi Hospital, Department of Mother-Child and Biology-Genetics, Verona University, Verona, Italy c APHP, Pediatric Sleep Disorders Center, Robert Debre´ Hospital, Paris, France d APHP, Sleep Disorders Center, Pitie´-Salpeˆtrie`re Hospital, Paris, France
Received 8 August 2007; received in revised form 16 October 2007; accepted 18 October 2007 Available online 4 March 2008
Abstract An 11-year-old girl was referred for an irresistible urge to move her legs associated with uncomfortable sensations. She was diagnosed with definite Restless Legs Syndrome (RLS) according to 2003 NIH criteria. The IRLSSG severity scale score was 31 (very severe). The girl also presented with dysthymic disorder according to DSM-IV criteria, as confirmed by the semi-structured interview Kiddie-SADS-PL. The score on the Children Depression Inventory (CDI) was in the clinical range (21). The total score on the Sleep Disturbance Scale for Children (SDSC) was 100. A standard PSG revealed a periodic limb movement index of 16.5, indicating that the child also presented with Periodic Limb Movements Disorder. The girl was treated with ropinirole (a D2/D3 dopamine agonist). After 3 months of treatment (0.50 mg/day at 8.00 PM), RLS, as well as depressive symptoms, remarkably improved, as suggested by the improvement in the IRLSSG severity and CDI scores (14 and 4, respectively). No side effects were reported. The total score on the SDSC also improved (73). The PLM index did not remarkably change. We strongly recommend double blind, randomized, controlled studies to gain insight into the effective treatment strategies for RLS and depression when they coexist in children. Ó 2007 Elsevier B.V. All rights reserved. Keywords: RLS; PLMS; Depression; Ropinirole; Iron; Childhood
1. Introduction Although Restless Legs Syndrome (RLS) has been traditionally considered a disorder of middle to older age, it may occur in children [1]. In 2003, the International Restless Legs Syndrome Study Group (IRLSSG) proposed a set of criteria specific for children [1]. In the first population-based study using these criteria, Picchietti et al. recently found that 1.9% of 8- to 11-year-olds
* Corresponding author. Address: Service de Psychopathologie, de l’Enfant et de l’Adolescent, Hoˆpital Robert Debre´, 48 Boulevard Se´rurier, 75019 Paris, France. Tel.: +33 140032263; fax: +33 140032297. E-mail addresses: [email protected], [email protected] (S. Cortese).
1389-9457/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2007.10.023
and 2.0% of 12- to 17-year-olds presented with definite RLS [2]. At present, evidence on the pharmacological management of RLS in childhood is limited. Case reports have documented the effectiveness of levodopa/carbidopa [3], pergolide [3], ropinirole [4], and pramipexole [5]. Recent evidence from adult studies suggests an interesting but still poorly understood association between RLS and depressive symptoms [6]. To date, this relationship has been scarcely investigated in childhood. So far no evidence-based guidelines are available for the treatment of patients (adults and children) with both RLS and depressive disorders. To gain insight into possible strategies for the management of RLS and depression in childhood, we report
260
S. Cortese et al. / Sleep Medicine 10 (2009) 259–261
the effectiveness of ropinirole (a D2/D3 dopamine agonist) for both RLS and depressive symptoms in an 11year-old girl.
Table 1 Overnight polysomnographic findings before and after 3 months of treatment (ropinirole 0.50 mg/day)
2. Case
TSP (min) TST (min) SE (% of TST) SOL (min) REM onset latency (min) SWS (%TST) REM (%TST) Respiratory index PLM index (/h TST) PLMa index (/h TST) Mean SpO2 (%) SpO2 nadir (%)
The girl was referred to our unit at the age of 11 for an irresistible urge to move her legs associated with uncomfortable sensations, developed after heart surgery at the age of 9 years. The medical history of the child previous to the surgical intervention was normal. No drugs were prescribed to the child previous to the surgical intervention. At the age of 9, the child was diagnosed with an interatrial communication which required surgery. About five days after surgery, the child began to complain of bilaterally uncomfortable sensations in her legs, associated with an urge to move her legs in order to alleviate these sensations. The sensations persisted every day after surgery. The symptomatology was completely absent before the intervention. The child’s mother met RLS criteria. The grandmother complained of similar sensations, but, unfortunately, no other data could be obtained on the grandmother. The father of the patient, her brother, and her sister presented no RLS symptoms. When the patient consulted our Unit, her symptomatology was impairing. She was free from drugs known to cause RLS [1]. The neurological examination was normal. Her Tanner stage was T3. The child met IRLSSG criteria for the diagnosis of definite RLS in children [1]. The IRLSSG severity scale [7] score was 31 (very severe). The T-scores on the Sleep Disturbance Scale for Children (SDSC) [8] were as follows: difficulty in initiating and maintaining sleep (DIMS): 100; sleep breathing disorders (SBD): 45; arousal disorders (DA): 58; sleep– wake transition disorders (SWTD): 91; disorders of excessive somnolence (DOES): 77; sleep hyperhydrosis (SHY): 63; total score (TOT): 100. During the first consultation, the parents reported a dysthymic mood in the patient from almost 18 months. The semi-structured interview Kiddie-SADSPL [9] confirmed the diagnosis of dysthymic disorder according to DSM-IV criteria. The score on the Children Depression Inventory (CDI) [10] (a self-reported questionnaire assessing depressive symptoms in childhood) was 21 (the cut-off for identifying symptoms in the clinical range is 19). No suicidal ideation was reported. Serum ferritin, measured one week after the first consultation, was 19 ng/mL (normal reference range: 15– 40 ng/mL). Haemoglobin level was in the normal range (12.5 g/dL). A standard overnight multichannel PSG was performed one week after the first consultation (Table 1). The periodic limb movements index was 16.5, indicating
Before
After
508 457 89.8 6.0 100.0 29.1 15.7 0.0 16.5 5.4 97.8 95.0
481 411 85.4 6.0 240.0 39.4 14.3 1.0 13.7 5.8 99.0 93.0
TSP, total sleep period; TST, total sleep time; SE, sleep efficiency; SOL, sleep onset latency; SWS, slow wave sleep; REM, rapid eyes movements; PLM, periodic limb movements; PLMa, periodic limb movements with arousals.
that the child also presented with Periodic Limb Movements Disorder (PLMD). After discussing common sleep hygiene rules, we first proposed iron supplementation (ferrous sulphate, 80 mg/day of iron element). After two months, the girl reported only a mild improvement of RLS symptoms (IRLSSG severity scale: 27). No remarkable changes in her mood were found (CDI score: 20). She did not want to engage in psychotherapy. Therefore, after obtaining the parents’ and patient’s agreement, ropinirole was started (0.25 mg/day at 8 p.m.). We did not consider an antidepressant as the first pharmacological option since RLS symptomatology seemed much more impairing than depressive symptoms. Iron supplementation was continued since serum ferritin levels were not remarkably increased (26 ng/mL). After 1 month, a moderate improvement in RLS and depressive symptoms was reported. IRLSSG severity score was 22. CDI score decreased to 18. Ropinirole was well tolerated, with no side effects reported. Serum ferritin levels slightly increased (31 ng/mL). Ropinirole was increased to 0.50 mg/day at 8 p.m. After three months, RLS, as well as depressive symptoms, remarkably improved: IRLSSG severity and CDI scores were 14 and 4, respectively. The T-scores on the SDSC were as follows: DIMS: 82; SBD: 45; DA: 70; SWTD: 58; DOES: 69; SHY: 51; TOT: 73. Serum ferritin levels were 44 ng/mL. The findings on a second PSG are reported in Table 1. The PSG variables did not remarkably change. However, a reduction of periodic limb movements in SWS was found, contributing, in part, to the increase of SWS total time. No side effects were reported by the girl nor by her parents. Vital signs (blood pressure, pulse, and temperature), monitored weekly in the first month and monthly thereafter, were normal.
S. Cortese et al. / Sleep Medicine 10 (2009) 259–261
3. Discussion This is the first case showing the effectiveness and good tolerability of ropinirole for both RLS and depressive symptoms in a young girl. Since RLS preceded depressive mood, which improved after the treatment of RLS, it is possible that RLS contributed to the patient’s depression through its adverse effects on sleep and daytime alertness. Interestingly, the scores on the SDSC in our patient decreased after six months of treatment. It is unlikely that sleep disruption caused by periodic limb movements contributed to depression in our patient since the PLMS index and the PLMS associated with arousals index did not change significantly during treatment. Since periodicity of limb movements is not a consistent finding in childhood [11], we suggest that future studies should investigate the effect of dopaminergic agents on aperiodic limb movements. Another hypothesis explaining how RLS led to depression in our patient is that RLS, like other chronic conditions, induces pain and stress, which, in turn, leads to depressive symptoms associated with low self-esteem. Since depressive symptoms were not present before surgery, we can not rule out the hypothesis that the mood disorder was in part reactive to the past heart surgery. However, since mood improved after the treatment of RLS, we speculate that RLS at least contributed to depressive symptoms. It is also possible that RLS and depression shared common pathophysiological patterns, which may have been the target of the medication. Interestingly, REM latency increased during treatment. Indeed, it is possible that ropinirole increased REM latency, as found in a previous report in adults [12]. The increase of REM latency could be related to the improvement of depressive symptoms, since a reduced REM latency has been reported in childhood depression, paralleling the findings in adults [13]. Independently from the explication of the improvement of RLS and mood, our case suggests that the successful treatment of both RLS and depressive symptoms may be obtained using only RLS treatment. This is of relevance since the common medications used to treat depression (i.e., SSRIs) may aggravate RLS, although recent evidence does not support this statement [14]. We strongly recommend double blind, randomized, controlled studies to gain insight into the effective treat-
261
ment strategies for RLS and depression when they coexist in children.
References [1] Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101–19. [2] Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L. Restless legs syndrome: prevalence and impact in children and adolescents-the Peds REST study. Pediatrics 2007;120:253–66. [3] Walters AS, Mandelbaum DE, Lewin DS, Kugler S, England SJ, Miller M. Dopaminergic therapy in children with restless legs/ periodic limb movements in sleep and ADHD dopaminergic therapy study group. Pediatr Neurol 2000;22:182–6. [4] Konofal E, Arnulf I, Lecendreux M, Mouren MC. Ropinirole in a child with attention-deficit hyperactivity disorder and restless legs syndrome. Pediatr Neurol 2005;32:350–1. [5] Guilleminault C, Palombini L, Pelayo R, Chervin RD. Sleepwalking and sleep terrors in prepubertal children: what triggers them? Pediatrics 2003;111:e17–25. [6] Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep 2005;28:891–8. [7] Hening A, Walters AS, Rosen R. The international RLS study group rating scale: a reliable and valid instrument for assessing severity of the restless legs syndrome. Neurology Suppl 2001;56:A4. [8] Bruni O, Ottaviano S, Guidetti V, Romoli M, Innocenzi M, Cortesi F, et al. The sleep disturbance scale for children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence. J Sleep Res 1996;5:251–61. [9] Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997;36:980–8. [10] Kovacs M. The children’s depression, inventory (CDI). Psychopharmacol Bull 1985;21:995–8. [11] Pennestri MH, Whittom S, Adam B, Petit D, Carrier J, Montplaisir J. PLMS and PLMW in healthy subjects as a function of age: prevalence and interval distribution. Sleep 2006;29:1183–7. [12] Saletu M, Anderer P, Saletu B, Hauer C, Mandl M, Semler B, et al. Sleep laboratory studies in periodic limb movement disorder (PLMD) patients as compared with normals and acute effects of ropinirole. Hum Psychopharmacol 2001;16:177–87. [13] Ivanenko A, Crabtree VM, Gozal D. Sleep and depression in children and adolescents. Sleep Med Rev 2005;9:115–29. [14] Brown LK, Dedrick DL, Doggett JW, Guido PS. Antidepressant medication use and restless legs syndrome in patients presenting with insomnia. Sleep Med 2005;6:443–50.