European Journal of Pediatrics

, Volume 175, Issue 1, pp 9–18 | Cite as

Psychotropic treatments in Prader-Willi syndrome: a critical review of published literature

  • O. BonnotEmail author
  • D. Cohen
  • D. Thuilleaux
  • A. Consoli
  • S. Cabal
  • M. Tauber


Prader-Willi syndrome (PWS) is a rare genetic syndrome. The phenotype includes moderate to intellectual disability, dysmorphia, obesity, and behavioral disturbances (e.g., hetero and self-injurious behaviors, hyperphagia, psychosis). Psychotropic medications are widely prescribed in PWS for symptomatic control. We conducted a systematic review of published literature to examine psychotropic medications used in PWS. MEDLINE was searched to identify articles published between January 1967 and December 2014 using key words related to pharmacological treatments and PWS. Articles with original data were included based on a standardized four-step selection process. The identification of studies led to 241 records. All selected articles were evaluated for case descriptions (PWS and behavioral signs) and treatment (type, titration, efficiency, and side effects). Overall, 102 patients were included in these studies. Treatment involved risperidone (three reports, n = 11 patients), fluoxetine (five/n = 6), naltrexone (two/n = 2), topiramate (two/n = 16), fluvoxamine (one/n = 1), mazindol (one/n = 2), N-acetyl cysteine (one/n = 35), rimonabant (one/n = 15), and fenfluramine (one/n = 15).

Conclusion: We identified promising treatment effects with topiramate for self-injury and impulsive/aggressive behaviors, risperidone for psychotic symptoms associated with uniparental disomy (UPD), and N-acetyl cysteine for skin picking. The pharmacological approach of behavioral impairment in PWS has been poorly investigated to date. Further randomized controlled studies are warranted.

What is Known:

Behavioral disturbances in Prader-Willi syndrome including aggressive reactions, skin picking, and hyperphagia might be very difficult to manage.

Antipsychotic drugs are widely prescribed, but weight gain and increased appetite are their major side effects.

What is New:

Topiramate might be efficient for self-injury and impulsive/aggressive behaviors, N-acetyl cysteine is apromising treatment for skin picking and Antidepressants are indicated for OCD symptoms.

Risperidone is indicated in case of psychotic symptoms mainly associated with uniparental disomy.


Prader-Willi syndrome Antipsychotic Topiramate Risperidone Methylphenidate Antidepressor 



Aberrant behavior checklist


Cognitive behavioral therapy


Clinical global impression




Obsessive compulsive behavior


Retrospective overt aggressive score


Self-injury restraint checklist


Uniparental disomy


Yale Brown obsessive compulsive subscale


Authors’ contribution

OB, DC, and MT conceived of the study and participated in its design and coordination and helped to draft the manuscript. DC made the most important contribution to this second part. All authors (OB, DC, AC, SC, DT, and MT) did participate in the meetings regarding the bibliography search, the reading of the selected articles, and the related discussions. OB, DC, DT, and MT participated in the design of the study. All authors read and approved the final manuscript.

Compliance with ethical standards

Research is not involving human participant.

This article does not contain any studies with human participant performed by any of the authors. There is no human or animal material use in this study and no personal data of any kind. Our work is entirely based on literature search.

Informed consent

Informed consent was not relevant. No informed consent.

Conflict of interest

The authors declare that they have no competing interests.


This study was funded by a Grant of French Ministry of Health (PHRC 2010-AOM1008).

Information’s regarding authors

We are a group of psychiatrists and pediatrician implicated in rare disease with psychiatric symptoms, including PWS. We are working in a national reference network in this field funded by the French government and European Union. MT, DT, and SC are working in the National Reference Center for PWS, and OB, DC, and AC are working in the National Reference Center for Psychiatric Symptoms of Rare Disease.


  1. 1.
    Adams S, Penton-Voak IS, Harmer CJ, Holmes EA, Munafo MR (2013) Effects of emotion recognition training on mood among individuals with high levels of depressive symptoms: study protocol for a randomised controlled trial. Trials 14:161. doi: 10.1186/1745-6215-14-161 PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Amrouche-Mekkioui I, Djerdjouri B (2012) N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice. Eur J Pharmacol 691:209–217. doi: 10.1016/j.ejphar.2012.06.014 CrossRefPubMedGoogle Scholar
  3. 3.
    Araki S, Ohji T, Shiota N, Dobashi K, Shimono M, Shirahata A (2010) Successful risperidone treatment for behavioral disturbances in Prader-Willi syndrome. Pediatrics international : official journal of the Japan Pediatric Society 52:e1–e3. doi: 10.1111/j.1442-200X.2009.02996.x CrossRefGoogle Scholar
  4. 4.
    Arbaizar B, Gomez-Acebo I, Llorca J (2008) Efficacy of topiramate in bulimia nervosa and binge-eating disorder: a systematic review. Gen Hosp Psychiatry 30:471–475CrossRefPubMedGoogle Scholar
  5. 5.
    Banga A, Connor DF (2012) Effectiveness of naltrexone for treating pathologic skin picking behavior in an adolescent with Prader-Willi syndrome. J Child Adolesc Psychopharmacol 22:396–398. doi: 10.1089/cap.2012.0028 CrossRefPubMedGoogle Scholar
  6. 6.
    Beardsmore A, Dorman T, Cooper SA, Webb T (1998) Affective psychosis and Prader-Willi syndrome. J Intellect Disabil Res 42(Pt 6):463–471CrossRefPubMedGoogle Scholar
  7. 7.
    Benarroch F, Hirsch HJ, Genstil L, Landau YE, Gross-Tsur V (2007) Prader-Willi syndrome: medical prevention and behavioral challenges. Child Adolesc Psychiatr Clin N Am 16:695–708. doi: 10.1016/j.chc.2007.03.007 CrossRefPubMedGoogle Scholar
  8. 8.
    Benjamin E, Buot-Smith T (1993) Naltrexone and fluoxetine in Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 32:870–873. doi: 10.1097/00004583-199307000-00025 CrossRefPubMedGoogle Scholar
  9. 9.
    Bertella L, Girelli L, Grugni G, Marchi S, Molinari E, Semenza C (2005) Mathematical skills in Prader-Willi Syndrome. J Intellect Disabil Res 49:159–169CrossRefPubMedGoogle Scholar
  10. 10.
    Biederman J, Faraone SV (2005) Attention-deficit hyperactivity disorder. Lancet 366:237–248. doi: 10.1016/S0140-6736(05)66915-2 CrossRefPubMedGoogle Scholar
  11. 11.
    Boer H, Holland A, Whittington J, Butler J, Webb T, Clarke D (2002) Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy. Lancet 359:135–136CrossRefPubMedGoogle Scholar
  12. 12.
    Buiting K (2010) Prader-Willi syndrome and Angelman syndrome. Am J Med Genet C: Semin Med Genet 154C:365–376. doi: 10.1002/ajmg.c.30273 CrossRefGoogle Scholar
  13. 13.
    Butler MG, Smith BK, Lee J, Gibson C, Schmoll C, Moore WV, Donnelly JE (2013) Effects of growth hormone treatment in adults with Prader-Willi syndrome. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 23:81–87. doi: 10.1016/j.ghir.2013.01.001 CrossRefGoogle Scholar
  14. 14.
    Clarke D (1998) Prader-Willi syndrome and psychotic symptoms: 2. A preliminary study of prevalence using the Psychopathology Assessment Schedule for Adults with Developmental Disability checklist. J Intellect Disabil Res 42(Pt 6):451–454CrossRefPubMedGoogle Scholar
  15. 15.
    Deb S, Unwin G, Deb T (2014) Characteristics and the trajectory of psychotropic medication use in general and antipsychotics in particular among adults with an intellectual disability who exhibit aggressive behaviour. J Intellect Disabil Res. doi: 10.1111/jir.12119
  16. 16.
    Dech B, Budow L (1991) The use of fluoxetine in an adolescent with Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 30:298–302. doi: 10.1097/00004583-199103000-00020 CrossRefPubMedGoogle Scholar
  17. 17.
    Dolengevich Segal H, Rodriguez Salgado B, Conejo Garcia A, San Sebastian Cabases J (2006) Efficacy of topiramate in children and adolescent with problems in impulse control: preliminary results. Actas Esp Psiquiatr 34:280–282PubMedGoogle Scholar
  18. 18.
    Duggan L, Brylewski J (1999) Effectiveness of antipsychotic medication in people with intellectual disability and schizophrenia: a systematic review. J Intellect Disabil Res 43(Pt 2):94–104CrossRefPubMedGoogle Scholar
  19. 19.
    Durst R, Rubin-Jabotinsky K, Raskin S, Katz G, Zislin J (2000) Risperidone in Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 39:545–546. doi: 10.1097/00004583-200005000-00004 CrossRefPubMedGoogle Scholar
  20. 20.
    Durst R, Rubin-Jabotinsky K, Raskin S, Katz G, Zislin J (2000) Risperidone in treating behavioural disturbances of Prader-Willi syndrome. Acta Psychiatr Scand 102:461–465CrossRefPubMedGoogle Scholar
  21. 21.
    Dykens EM, Roof E (2008) Behavior in Prader-Willi syndrome: relationship to genetic subtypes and age. J Child Psychol Psychiatry 49:1001–1008CrossRefPubMedGoogle Scholar
  22. 22.
    Fieldstone A, Zipf WB, Sarter MF, Berntson GG (1998) Food intake in Prader-Willi syndrome and controls with obesity after administration of a benzodiazepine receptor agonist. Obes Res 6:29–33CrossRefPubMedGoogle Scholar
  23. 23.
    Francey SM, Nelson B, Thompson A, Parker AG, Kerr M, Macneil C, Fraser R, Hughes F, Crisp K, Harrigan S, Wood SJ, Berk M, McGorry PD (2010) Who needs antipsychotic medication in the earliest stages of psychosis? A reconsideration of benefits, risks, neurobiology and ethics in the era of early intervention. Schizophr Res 119:1–10CrossRefPubMedGoogle Scholar
  24. 24.
    Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M, speakers contributors at the Second Expert Meeting of the Comprehensive Care of Patients with PWS (2008) Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab 93:4183–4197. doi: 10.1210/jc.2008-0649 CrossRefGoogle Scholar
  25. 25.
    Hassler F, Reis O (2010) Pharmacotherapy of disruptive behavior in mentally retarded subjects: a review of the current literature. Dev Disabil Res Rev 16:265–272. doi: 10.1002/ddrr.119 CrossRefPubMedGoogle Scholar
  26. 26.
    Herguner S, Mukaddes NM (2007) Psychosis associated with fluoxetine in Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 46:944–945. doi: 10.1097/chi.0b013e318068fbed CrossRefPubMedGoogle Scholar
  27. 27.
    Itoh M, Koeda T, Ohno K, Takeshita K (1995) Effects of mazindol in two patients with Prader-Willi syndrome. Pediatr Neurol 13:349–351CrossRefPubMedGoogle Scholar
  28. 28.
    Jauregi J, Arias C, Vegas O, Alen F, Martinez S, Copet P, Thuilleaux D (2007) A neuropsychological assessment of frontal cognitive functions in Prader-Willi syndrome. J Intellect Disabil Res 51:350–365CrossRefPubMedGoogle Scholar
  29. 29.
    Kennedy GM, Lhatoo SD (2008) CNS adverse events associated with antiepileptic drugs. CNS Drugs 22:739–760CrossRefPubMedGoogle Scholar
  30. 30.
    Khan A, Faught E, Gilliam F, Kuzniecky R (1999) Acute psychotic symptoms induced by topiramate. Seizure 8:235–237CrossRefPubMedGoogle Scholar
  31. 31.
    Kohn Y, Weizman A, Apter A (2001) Aggravation of food-related behavior in an adolescent with Prader-Willi syndrome treated with fluvoxamine and fluoxetine. Int J Eat Disord 30:113–117CrossRefPubMedGoogle Scholar
  32. 32.
    Kyriakides M, Silverstone T, Jeffcoate W, Laurance B (1980) Effect of naloxone on hyperphagia in Prader-Willi syndrome. Lancet 1:876–877CrossRefPubMedGoogle Scholar
  33. 33.
    Lee YJ, Marcu S, Berall G, Shapiro CM (2011) Tryptophan for the treatment of excessive daytime sleepiness in Prader-Willi syndrome. Indian Pediatr 48:319–321CrossRefPubMedGoogle Scholar
  34. 34.
    Lin G, Lawrence R (2006) Pediatric case report of topiramate toxicity. Clin Toxicol (Phila) 44:67–69CrossRefGoogle Scholar
  35. 35.
    Matthews SC, Miller BP (2001) Auditory hallucinations associated with topiramate. J Clin Psychiatry 62:653CrossRefPubMedGoogle Scholar
  36. 36.
    Miller JL, Angulo M (2014) An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome. Am J Med Genet A 164:421–424. doi: 10.1002/ajmg.a.36306 CrossRefGoogle Scholar
  37. 37.
    Morgan JR, Storch EA, Woods DW, Bodzin D, Lewin AB, Murphy TK (2010) A preliminary analysis of the phenomenology of skin-picking in Prader-Willi syndrome. Child Psychiatry Hum Dev 41:448–463. doi: 10.1007/s10578-010-0180-7 CrossRefPubMedGoogle Scholar
  38. 38.
    Motaghedi R, Lipman EG, Hogg JE, Christos PJ, Vogiatzi MG, Angulo MA (2011) Psychiatric adverse effects of rimonobant in adults with Prader Willi syndrome. Eur J Med Genet 54:14–18. doi: 10.1016/j.ejmg.2010.09.015 PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Mula M, Trimble MR, Lhatoo SD, Sander JW (2003) Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia 44:659–663CrossRefPubMedGoogle Scholar
  40. 40.
  41. 41.
    Rana F, Gormez A, Varghese S (2013) Pharmacological interventions for self-injurious behaviour in adults with intellectual disabilities. The Cochrane database of systematic reviews 4:CD009084. doi: 10.1002/14651858.CD009084.pub2 PubMedGoogle Scholar
  42. 42.
    Reas DL, Grilo CM (2008) Review and meta-analysis of pharmacotherapy for binge-eating disorder. Obesity (Silver Spring) 16:2024–2038CrossRefGoogle Scholar
  43. 43.
    Reis AD, Castro LA, Faria R, Laranjeira R (2008) Craving decrease with topiramate in outpatient treatment for cocaine dependence: an open label trial. Rev Bras Psiquiatr 30:132–135CrossRefPubMedGoogle Scholar
  44. 44.
    Schepis C, Failla P, Siragusa M, Palazzo R, Romano C (1998) Failure of fluoxetine to modify the skin-picking behaviour of Prader-Willi syndrome. Australas J Dermatol 39:57–58CrossRefPubMedGoogle Scholar
  45. 45.
    Selikowitz M, Sunman J, Pendergast A, Wright S (1990) Fenfluramine in Prader-Willi syndrome: a double blind, placebo controlled trial. Arch Dis Child 65:112–114PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Semenza C, Pignatti R, Bertella L, Ceriani F, Mori I, Molinari E, Giardino D, Malvestiti F, Grugni G (2008) Genetics and mathematics: evidence from Prader-Willi syndrome. Neuropsychologia 46:206–212CrossRefPubMedGoogle Scholar
  47. 47.
    Shapira NA, Lessig MC, Lewis MH, Goodman WK, Driscoll DJ (2004) Effects of topiramate in adults with Prader-Willi syndrome. American journal of mental retardation : AJMR 109:301–309. doi: 10.1352/0895-8017(2004)109<301:EOTIAW>2.0.CO;2 CrossRefPubMedGoogle Scholar
  48. 48.
    Shapira NA, Lessig MC, Murphy TK, Driscoll DJ, Goodman WK (2002) Topiramate attenuates self-injurious behaviour in Prader-Willi Syndrome. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum 5:141–145. doi: 10.1017/S1461145702002833 Google Scholar
  49. 49.
    Sinnema M, Boer H, Collin P, Maaskant MA, van Roozendaal KE, Schrander-Stumpel CT, Curfs LM (2011) Psychiatric illness in a cohort of adults with Prader-Willi syndrome. Res Dev Disabil 32:1729–1735. doi: 10.1016/j.ridd.2011.02.027 CrossRefPubMedGoogle Scholar
  50. 50.
    Skokauskas N, Sweeny E, Meehan J, Gallagher L (2012) Mental health problems in children with prader-willi syndrome. Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l’Academie canadienne de psychiatrie de l’enfant et de l’adolescent 21:194–203PubMedGoogle Scholar
  51. 51.
    Smathers SA, Wilson JG, Nigro MA (2003) Topiramate effectiveness in Prader-Willi syndrome. Pediatr Neurol 28:130–133CrossRefPubMedGoogle Scholar
  52. 52.
    Soni S, Whittington J, Holland AJ, Webb T, Maina E, Boer H, Clarke D (2007) The course and outcome of psychiatric illness in people with Prader-Willi syndrome: implications for management and treatment. J Intellect Disabil Res 51:32–42. doi: 10.1111/j.1365-2788.2006.00895.x CrossRefPubMedGoogle Scholar
  53. 53.
    Soni S, Whittington J, Holland AJ, Webb T, Maina EN, Boer H, Clarke D (2008) The phenomenology and diagnosis of psychiatric illness in people with Prader-Willi syndrome. Psychol Med 38:1505–1514PubMedGoogle Scholar
  54. 54.
    Stella F, Caetano D, Cendes F, Guerreiro CA (2002) Acute psychotic disorders induced by topiramate: report of two cases. Arq Neuropsiquiatr 60:285–287CrossRefPubMedGoogle Scholar
  55. 55.
    Unwin GL, Deb S (2011) Efficacy of atypical antipsychotic medication in the management of behaviour problems in children with intellectual disabilities and borderline intelligence: a systematic review. Res Dev Disabil 32:2121–2133. doi: 10.1016/j.ridd.2011.07.031 CrossRefPubMedGoogle Scholar
  56. 56.
    Van Borsel J, Defloor T, Curfs LM (2007) Expressive language in persons with Prader-Willi syndrome. Genet Couns 18:17–28PubMedGoogle Scholar
  57. 57.
    Vogels A, Matthijs G, Legius E, Devriendt K, Fryns JP (2003) Chromosome 15 maternal uniparental disomy and psychosis in Prader-Willi syndrome. J Med Genet 40:72–73PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Whitman BY, Accardo P (1987) Emotional symptoms in Prader-Willi syndrome adolescents. Am J Med Genet 28:897–905CrossRefPubMedGoogle Scholar
  59. 59.
    Whittington J, Holland A, Webb T, Butler J, Clarke D, Boer H (2004) Academic underachievement by people with Prader-Willi syndrome. J Intellect Disabil Res 48:188–200CrossRefPubMedGoogle Scholar
  60. 60.
    Wu K, Hanna GL, Easter P, Kennedy JL, Rosenberg DR, Arnold PD (2013) Glutamate system genes and brain volume alterations in pediatric obsessive-compulsive disorder: a preliminary study. Psychiatry Res 211:214–220. doi: 10.1016/j.pscychresns.2012.07.003 PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • O. Bonnot
    • 1
    Email author
  • D. Cohen
    • 2
  • D. Thuilleaux
    • 3
  • A. Consoli
    • 2
  • S. Cabal
    • 5
  • M. Tauber
    • 4
  1. 1.Child and Adolescent Psychiatry DepartmentLPL-University Hospital Nantes and GDR 3557, Psychiatric InstituteNantesFrance
  2. 2.Child and Adolescent Psychiatry Department, Groupe Hospitalier Pitie Salpetriere, APHPParis & Centre for Rare Diseases with Psychiatric Symptoms, APHPParisFrance
  3. 3.Rare Disease with Psychiatric Symptoms DepartmentHôpital Mari, APHPHendayeFrance
  4. 4.Pediatric DepartmentUniversity Hospital Toulouse & Rare Disease Center for Prader Willi Syndrome, CHU de ToulouseToulouseFrance
  5. 5.Child and Adolescent Psychiatry DepartmentCHU de ToulouseToulouseFrance

Personalised recommendations