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MORE ON VALPROATE AND POLYCYSTIC OVARIES
LETTERS TO T HE E D IT O R
question for which there is inadequate information and doing both the children and the field a d isservice. Gabrielle A. Carlson, M.D. D ivision of C hild and Adolescent Psychiatr y School of Medicine State University of New York Stony Brook Biederma n J. Klein RG . Pine DS. Klein D F ( 199 8) , Resolved: ma nia is mistaken for AD HD in prepubert al childre n. ] Am Acad Child Adolesc Psychiatry 37:1091-10 99 Ca plan R (1998), Communication deficits in children: is th ought disorder specific to schizophre nia? Presented at Annual Meeting of the American Academy of C hild and Adolescent Psychiatry. Anaheim , CA. O ctober 28 Carlso n GA. Bremer EJ (1998) Youth vs ad ult onset man ia: comorbidity o r confusion? Present ed at Annual Meet ing of the Amer ican Academy of C hild and Adolescent Psychiatry. Anaheim. CA. O cto ber 28 Carlson GA, Kelly KK (1998), Man ic sympto ms in psychiatr ically hospit alized child ren: what do the y mean ?] Affier Disord 5 1:123-1 35 Clo ninger R (1987). A systematic meth od for clinical description and classification of personality variant s. Arch Gen Psychiatry 44:573-5 88 McElroy SL. Soutullo CA, Beckm an DA. Taylor P. Jr. Keck PE. Jr (199 8), DSM-IV intcrm iu enr explosive d isord er: a report of 27 csses.] Clin Psy-
tion, the rate of PCO in obese epileptic women not taking valproate was far less. We do not believe Isojarvi and colleagues' data conclusively establishes valproate as the culprit, but his data strongl y suggest that caution is warranted! We agree with Dr. Eberle that withholding valproate from seriously ill girls is not sensible. Indeed , valproate can be strikingl y effective when all else has failed. However, we feel that other mood-stabilizing medications should be considered first, particularly for longer-term prophylactic treatment. We are surpr ised and dism ayed that the manufacturer of divalproex, Abbott Laboratories, is not conducting prospective studies that would shed light on this extremely important question . We are also con cern ed that the Food and Drug Administration has not taken a leadership role by requ iring such studies be done. This is particularly troubling given that we are now in an enlightened era in which issues specific to women's health are (sup posed ly) receiving much-needed emphasis. Hugh E Johnston, M .D. Child Psychoph armacology Information Service University of Wisconsin Medical School Madison
chiatry 59:203- 210 Tannock R, Schachar R (1996), Executuve dysfunction as an und erlying mechanism of behavior and language probl ems in attention deficit hyper ac t ivity disorder. In: Language, Learning and Behavior Disorders: Deuelopmm tal, Biological and Clinical Perspectives, Beirchrnan JH, Cohen N . Konsrantareas MM , Tanock R. eds. New York: Ca mbridge University Press, pp 128-1 55
MORE ON VALPROATE AND POLYCYSTIC OVARIES
To the Editor: In this Journ al. D r. Eberle (19 98) recently co m mented on data linking valproate to polycystic ovaries (PCO) . We would like to add our comments to the dialogue. We have been keenly interested in the issue of gynecological effects of valproate (and divalproex ) in young girls and have advocated th at thi s drug be considered a second-line agent (johnston et al., 1997) for the treatment of bipolar disorder in girl s. Our recommendation is based largel y on Isojarvi and colleagues' (1993) finding of extraordinarily high rates of obesity, menstrual disturbance, and PCO in women taking valproate for epilepsy. It is also based on the product labeling for divalproex (Depakotc'"), which States that it is indicated for acut e treatment of mania. Currently, lithium is the only medication approved for prophylaxis of mania. We disagree with Dr. Eberle's assertion that "there is no eviden ce that valp roate di rectly causes PCO. " It app ears that 100% of the women in the Isojarvi et al. stu dy who had started valproate before age 20 and who were obese had PCO. While it is true that PCO are associated with obesity (Pasquali and Casimirri, 1993) , and with epilepsy (Bilo et al., 1988), it is improbable that these factors could account for such a striking finding. Ind eed, in Isojarvi and colleagues' study popula-
354
Bilo L, Meo R, Napp i C et al. (1988 ). Reproductive endocrine d isorder s in wo men with primary generalized ep ilepsy. Epilepsia 29:612- 619 Eberle AJ (1998) . Valproate and polycystic ovaries (lett er). ] Am Acad Child Adolesc Psychiatry 37:1009 Isojarvi JIT, Laatikainen TJ , Pakarinen AJ et al. (1993), Polycystic ovaries and hyperandrogenism in women taking valproate for epilep sy. N Eng] Med 329 :1383- 1388 johnston IF, Wi tkovsky MT, Fruehling JJ (199 7). Valproare, ovaries and teenage girls. Just the Facts 4(1) :1-2 Pasquali R. C asimi rri F (1993), The impact of obesity on hyperandrogen ism and polycystic ovary syndrome in premenopausal wom en. Clin Endocrinol (Oxf) 39: 1-1 6
SSRIs AND MOVEMENT DISORDERS
To the Editor: Movement disorders have been associated with selective serotonin reuprake inh ibitors (SSRIs) (Bates et al., 1998; Gill et aI., 1997; Jon es-Fearing, 1996; Leo, 1996; Leonard et al., 199 7). However, although akath isia and extrapyramidal symptoms (EPS) have been widely reported in adults (Bates et al., 1998; Gill et aI., 1997; Jones-Fearing, 1996; Leo, 1996; Leonard et aI., 1997) extensive review of the literature identifies only 2 case reportS of children or adolescents without previous exposure to neuroleptics who have developed similar symptoms possibly attributable to SSRIs. A 12-year-old girl developed acute dystonia on her third day of Ruoxetine treat ment; thi s pat ient had recentl y discontinued nortriptyline and illicit amphetamine use that may have cont ributed to her symptoms (Jones-Fearing , 1996). Another case describes an l l-year-old girl with a left-sided dystonia which evolved into
J.
AM . ACA lJ . CH Il. D ADOL ESC. PSYC HI ATRY. _' 8 :4 . AP R I L 19 9 9
question for which there is inadequate information and doing both the children and the field a d isservice. Gabrielle A. Carlson, M.D. D ivision of C hild and Adolescent Psychiatr y School of Medicine State University of New York Stony Brook Biederma n J. Klein RG . Pine DS. Klein D F ( 199 8) , Resolved: ma nia is mistaken for AD HD in prepubert al childre n. ] Am Acad Child Adolesc Psychiatry 37:1091-10 99 Ca plan R (1998), Communication deficits in children: is th ought disorder specific to schizophre nia? Presented at Annual Meeting of the American Academy of C hild and Adolescent Psychiatry. Anaheim , CA. O ctober 28 Carlso n GA. Bremer EJ (1998) Youth vs ad ult onset man ia: comorbidity o r confusion? Present ed at Annual Meet ing of the Amer ican Academy of C hild and Adolescent Psychiatry. Anaheim. CA. O cto ber 28 Carlson GA, Kelly KK (1998), Man ic sympto ms in psychiatr ically hospit alized child ren: what do the y mean ?] Affier Disord 5 1:123-1 35 Clo ninger R (1987). A systematic meth od for clinical description and classification of personality variant s. Arch Gen Psychiatry 44:573-5 88 McElroy SL. Soutullo CA, Beckm an DA. Taylor P. Jr. Keck PE. Jr (199 8), DSM-IV intcrm iu enr explosive d isord er: a report of 27 csses.] Clin Psy-
tion, the rate of PCO in obese epileptic women not taking valproate was far less. We do not believe Isojarvi and colleagues' data conclusively establishes valproate as the culprit, but his data strongl y suggest that caution is warranted! We agree with Dr. Eberle that withholding valproate from seriously ill girls is not sensible. Indeed , valproate can be strikingl y effective when all else has failed. However, we feel that other mood-stabilizing medications should be considered first, particularly for longer-term prophylactic treatment. We are surpr ised and dism ayed that the manufacturer of divalproex, Abbott Laboratories, is not conducting prospective studies that would shed light on this extremely important question . We are also con cern ed that the Food and Drug Administration has not taken a leadership role by requ iring such studies be done. This is particularly troubling given that we are now in an enlightened era in which issues specific to women's health are (sup posed ly) receiving much-needed emphasis. Hugh E Johnston, M .D. Child Psychoph armacology Information Service University of Wisconsin Medical School Madison
chiatry 59:203- 210 Tannock R, Schachar R (1996), Executuve dysfunction as an und erlying mechanism of behavior and language probl ems in attention deficit hyper ac t ivity disorder. In: Language, Learning and Behavior Disorders: Deuelopmm tal, Biological and Clinical Perspectives, Beirchrnan JH, Cohen N . Konsrantareas MM , Tanock R. eds. New York: Ca mbridge University Press, pp 128-1 55
MORE ON VALPROATE AND POLYCYSTIC OVARIES
To the Editor: In this Journ al. D r. Eberle (19 98) recently co m mented on data linking valproate to polycystic ovaries (PCO) . We would like to add our comments to the dialogue. We have been keenly interested in the issue of gynecological effects of valproate (and divalproex ) in young girls and have advocated th at thi s drug be considered a second-line agent (johnston et al., 1997) for the treatment of bipolar disorder in girl s. Our recommendation is based largel y on Isojarvi and colleagues' (1993) finding of extraordinarily high rates of obesity, menstrual disturbance, and PCO in women taking valproate for epilepsy. It is also based on the product labeling for divalproex (Depakotc'"), which States that it is indicated for acut e treatment of mania. Currently, lithium is the only medication approved for prophylaxis of mania. We disagree with Dr. Eberle's assertion that "there is no eviden ce that valp roate di rectly causes PCO. " It app ears that 100% of the women in the Isojarvi et al. stu dy who had started valproate before age 20 and who were obese had PCO. While it is true that PCO are associated with obesity (Pasquali and Casimirri, 1993) , and with epilepsy (Bilo et al., 1988), it is improbable that these factors could account for such a striking finding. Ind eed, in Isojarvi and colleagues' study popula-
354
Bilo L, Meo R, Napp i C et al. (1988 ). Reproductive endocrine d isorder s in wo men with primary generalized ep ilepsy. Epilepsia 29:612- 619 Eberle AJ (1998) . Valproate and polycystic ovaries (lett er). ] Am Acad Child Adolesc Psychiatry 37:1009 Isojarvi JIT, Laatikainen TJ , Pakarinen AJ et al. (1993), Polycystic ovaries and hyperandrogenism in women taking valproate for epilep sy. N Eng] Med 329 :1383- 1388 johnston IF, Wi tkovsky MT, Fruehling JJ (199 7). Valproare, ovaries and teenage girls. Just the Facts 4(1) :1-2 Pasquali R. C asimi rri F (1993), The impact of obesity on hyperandrogen ism and polycystic ovary syndrome in premenopausal wom en. Clin Endocrinol (Oxf) 39: 1-1 6
SSRIs AND MOVEMENT DISORDERS
To the Editor: Movement disorders have been associated with selective serotonin reuprake inh ibitors (SSRIs) (Bates et al., 1998; Gill et aI., 1997; Jon es-Fearing, 1996; Leo, 1996; Leonard et al., 199 7). However, although akath isia and extrapyramidal symptoms (EPS) have been widely reported in adults (Bates et al., 1998; Gill et aI., 1997; Jones-Fearing, 1996; Leo, 1996; Leonard et aI., 1997) extensive review of the literature identifies only 2 case reportS of children or adolescents without previous exposure to neuroleptics who have developed similar symptoms possibly attributable to SSRIs. A 12-year-old girl developed acute dystonia on her third day of Ruoxetine treat ment; thi s pat ient had recentl y discontinued nortriptyline and illicit amphetamine use that may have cont ributed to her symptoms (Jones-Fearing , 1996). Another case describes an l l-year-old girl with a left-sided dystonia which evolved into
J.
AM . ACA lJ . CH Il. D ADOL ESC. PSYC HI ATRY. _' 8 :4 . AP R I L 19 9 9