Antidepressant‐Induced Manic Conversion: A Developmentally Informed Synthesis of the Literature

Achamallah, 1991, Mania induced by fluoxetine in an adolescent patient, Am. J. Psychiatry, 148, 1404, 10.1176/ajp.148.10.1404a Akiskal, 1995, Developmental pathways to bipolarity: Are juvenile‐onset depressions pre‐bipolar?, J. Am. Acad. Child Adolesc. Psychiatry, 34, 754, 10.1097/00004583-199506000-00016 Akiskal, 1983, Bipolar outcome in the course of depressive illness. Phenomenologic, familial, and pharmacologic predictors, J. Affect. Disord., 5, 115, 10.1016/0165-0327(83)90004-6 Alda, 2001, Genetic factors and treatment of mood disorders, Bipolar Disord., 3, 318, 10.1034/j.1399-5618.2001.30606.x Altshuler, 2003, Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1‐year follow‐up, Am. J. Psychiatry, 160, 1252, 10.1176/appi.ajp.160.7.1252 Altshuler, 1995, Antidepressant‐induced mania and cycle acceleration: A controversy revisited, Am. J. Psychiatry, 152, 1130, 10.1176/ajp.152.8.1130 Amsterdam, 1998, Efficacy and safety of fluoxetine in treating bipolar II major depressive episode, J. Clin. Psychopharmacol., 18, 435, 10.1097/00004714-199812000-00003 Amsterdam, 2004, Short‐term fluoxetine monotherapy for bipolar type II or bipolar NOS major depression—low manic switch rate, Bipolar Disord., 6, 75, 10.1046/j.1399-5618.2003.00083.x Ansorge, 2004, Early‐life blockade of the 5‐HT transporter alters emotional behavior in adult mice, Science, 306, 879, 10.1126/science.1101678 APA, 1994, Practice guideline for the treatment of patients with bipolar disorder, Am. J. Psychiatry, 151, 1, 10.1176/ajp.151.12.1 APA, 2000, Practice guideline for the treatment of patients with major depressive disorder (revision), Am. J. Psychiatry, 157, 1 Biederman, 2000, Therapeutic dilemmas in the pharmacotherapy of bipolar depression in the young, J. Child Adolesc. Psychopharmacol., 10, 185, 10.1089/10445460050167296 Bijl, 1998, Prevalence of psychiatric disorder in the general population: Results of The Netherlands Mental Health Survey and Incidence Study (NEMESIS), Soc. Psychiatry Psychiatr. Epidemiol., 33, 587, 10.1007/s001270050098 Birmaher, 1998, Summary of the practice parameters for the assessment and treatment of children and adolescents with depressive disorders, J. Am. Acad. Child Adolesc. Psychiatry, 37, 1234, 10.1097/00004583-199811000-00029 Bottlender, 2001, Mood‐stabilisers reduce the risk of developing antidepressant‐induced maniform states in acute treatment of bipolar I depressed patients, J. Affect. Disord., 63, 79, 10.1016/S0165-0327(00)00172-5 Burke, 1990, Age at onset of selected mental disorders in five community populations, Arch. Gen. Psychiatry, 47, 511, 10.1001/archpsyc.1990.01810180011002 Carlson, 2003, Drug‐induced disinhibition in psychiatrically hospitalized children, J. Child Adolesc. Psychopharmacol., 13, 153, 10.1089/104454603322163871 Carrey, 2002, Noradrenergic and serotonergic neuroendocrine responses in prepubertal, peripubertal, and postpubertal rats pretreated with desipramine and sertraline, J. Am. Acad. Child Adolesc. Psychiatry, 41, 999, 10.1097/00004583-200208000-00019 Cicero, 2003, Antidepressant exposure in bipolar children, Psychiatry, 66, 317, 10.1521/psyc.66.4.317.25437 Cohen, 1985, Tolerance to therapeutic effects of antidepressants, Am. J. Psychiatry, 142, 489, 10.1176/ajp.142.4.489 Compton, 2004, Cognitive‐behavioral psychotherapy for anxiety and depressive disorders in children and adolescents: An evidence‐based medicine review, J. Am. Acad. Child Adolesc. Psychiatry, 43, 930, 10.1097/01.chi.0000127589.57468.bf Cook, 2001, Long‐term sertraline treatment of children and adolescents with obsessive‐compulsive disorder, J. Am. Acad. Child Adolesc. Psychiatry, 40, 1175, 10.1097/00004583-200110000-00011 Coryell, 2003, The long‐term course of rapid‐cycling bipolar disorder, Arch. Gen. Psychiatry, 60, 914, 10.1001/archpsyc.60.9.914 Costello, 1996, The Great Smoky Mountains Study of Youth. Goals, design, methods, and the prevalence of DSM‐III‐R disorders, Arch. Gen. Psychiatry, 53, 1129, 10.1001/archpsyc.1996.01830120067012 Coupland, 1996, Serotonin reuptake inhibitor withdrawal, J. Clin. Psychopharmacol., 16, 356, 10.1097/00004714-199610000-00003 Donaldson, 1989, Tolerance to phenelzine and subsequent refractory depression: Three cases, J. Clin. Psychiatry, 50, 33 Dunner, 1974, Clinical factors in lithium carbonate prophylaxis failure, Arch. Gen. Psychiatry, 30, 229, 10.1001/archpsyc.1974.01760080077013 Emslie, 2002, Fluoxetine for acute treatment of depression in children and adolescents: A placebo‐controlled, randomized clinical trial, J. Am. Acad. Child Adolesc. Psychiatry, 41, 1205, 10.1097/00004583-200210000-00010 Emslie, 1998, Fluoxetine in child and adolescent depression: Acute and maintenance treatment, Depress. Anxiety, 7, 32, 10.1002/(SICI)1520-6394(1998)7:1<32::AID-DA4>3.0.CO;2-7 Emslie, 1997, A double‐blind, randomized, placebo‐controlled trial of fluoxetine in children and adolescents with depression, Arch. Gen. Psychiatry, 54, 1031, 10.1001/archpsyc.1997.01830230069010 Faraone, 1997, Attention‐deficit hyperactivity disorder with bipolar disorder: A familial subtype?, J. Am. Acad. Child Adolesc. Psychiatry, 36, 1378, 10.1097/00004583-199710000-00020 Fava, 2003, Mania associated with venlafaxine discontinuation, Int. J. Neuropsychopharmacol., 6, 89, 10.1017/S1461145703003274 Fava, 1995, Relapse in patients on long‐term fluoxetine treatment: Response to increased fluoxetine dose, J. Clin. Psychiatry, 56, 52 Fava, 2002, Treatment approaches to major depressive disorder relapse. Part 2: Reinitiation of antidepressant treatment, Psychother. Psychosom., 71, 195, 10.1159/000063644 2004, FDA Public Health Advisory (October 15, 2004), Vol. 2004 Frances, 1998, The Expert Consensus Guidelines for treating depression in bipolar disorder, J. Clin. Psychiatry, 59, 73 Franchini, 1997, A double‐blind study of long‐term treatment with sertraline or fluvoxamine for prevention of highly recurrent unipolar depression, J. Clin. Psychiatry, 58, 104, 10.4088/JCP.v58n0303 Frank, 1990, Three‐year outcomes for maintenance therapies in recurrent depression, Arch. Gen. Psychiatry, 47, 1093, 10.1001/archpsyc.1990.01810240013002 Frazer, 1997, Pharmacology of antidepressants, J. Clin. Psychopharmacol., 17, 2S, 10.1097/00004714-199704001-00002 Geller, 1993, Effect of tricyclic antidepressants on switching to mania and on the onset of bipolarity in depressed 6‐ to 12‐year‐olds, J. Am. Acad. Child Adolesc. Psychiatry, 32, 43, 10.1097/00004583-199301000-00007 Geller, 2001, Fluoxetine treatment for obsessive‐compulsive disorder in children and adolescents: A placebo‐controlled clinical trial, J. Am. Acad. Child Adolesc. Psychiatry, 40, 773, 10.1097/00004583-200107000-00011 Geller, 2004, Four‐year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype, Arch. Gen. Psychiatry, 61, 459, 10.1001/archpsyc.61.5.459 Geller, 1998, Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra‐rapid or ultradian cycling, J. Affect. Disord., 51, 81, 10.1016/S0165-0327(98)00175-X Geller, 2001, Bipolar disorder at prospective follow‐up of adults who had prepubertal major depressive disorder, Am. J. Psychiatry, 158, 125, 10.1176/appi.ajp.158.1.125 Ghaemi, 2003, Antidepressants in bipolar disorder: The case for caution, Bipolar Disord., 5, 421, 10.1046/j.1399-5618.2003.00074.x Ghaemi, 2001, Effectiveness and safety of long‐term antidepressant treatment in bipolar disorder, J. Clin. Psychiatry, 62, 565, 10.4088/JCP.v62n07a12 Ghaemi, 2004, Antidepressant treatment in bipolar versus unipolar depression, Am. J. Psychiatry, 161, 163, 10.1176/appi.ajp.161.1.163 Ghaemi, 2003, Commentary, Int. J. Neuropsychopharmacol., 6, 303, 10.1017/S1461145703003626 Ghaziuddin, 1994, Mania induced by sertraline in a prepubertal child, Am. J. Psychiatry, 151, 944, 10.1176/ajp.151.6.944a Goddard, 1969, A permanent change in brain function resulting from daily electrical stimulation, Exp. Neurol., 25, 295, 10.1016/0014-4886(69)90128-9 Goldberg, 1994, Kindling in bipolar disorders: A longitudinal follow‐up study, Biol. Psychiatry, 35, 70, 10.1016/0006-3223(94)91169-X Goldberg, 2003, Antidepressant‐induced mania: An overview of current controversies, Bipolar Disord., 5, 407, 10.1046/j.1399-5618.2003.00067.x Goldberg, 2002, The association between substance abuse and antidepressant‐induced mania in bipolar disorder: A preliminary study, J. Clin. Psychiatry, 63, 791, 10.4088/JCP.v63n0907 Goldstein, 1999, Antidepressant discontinuation‐related mania: Critical prospective observation and theoretical implications in bipolar disorder, J. Clin. Psychiatry, 60, 563, 10.4088/JCP.v60n0811 Goodwin, 1990 Greenhill, 2003, Review of safety assessment methods used in pediatric psychopharmacology, J. Am. Acad. Child Adolesc. Psychiatry, 42, 627, 10.1097/01.CHI.0000046841.56865.37 Grubbs, 1997, SSRI‐induced mania, J. Am. Acad. Child Adolesc. Psychiatry, 36, 445, 10.1097/00004583-199704000-00003 Harrington, 1990, Adult outcomes of childhood and adolescent depression. I. Psychiatric status, Arch. Gen. Psychiatry, 47, 465, 10.1001/archpsyc.1990.01810170065010 Hazell, 1995, Efficacy of tricyclic drugs in treating child and adolescent depression: A meta‐analysis, BMG, 310, 897, 10.1136/bmj.310.6984.897 Heils, 1996, Allelic variation of human serotonin transporter gene expression, J. Neurochem., 66, 2621, 10.1046/j.1471-4159.1996.66062621.x Heimann, 1996, SSRI‐induced mania, J. Am. Acad. Child Adolesc. Psychiatry, 35, 4, 10.1097/00004583-199601000-00005 Henry, 2001, Antidepressant‐induced mania in bipolar patients: Identification of risk factors, J. Clin. Psychiatry, 62, 249, 10.4088/JCP.v62n0406 Hirschfeld, 2001, Clinical importance of long‐term antidepressant treatment, Br. J. Psychiatry, 42, S4, 10.1192/bjp.179.42.s4 Holmes, 2003, Abnormal anxiety‐related behavior in serotonin transporter null mutant mice: The influence of genetic background, Genes Brain Behav., 2, 365, 10.1046/j.1601-1848.2003.00050.x Howland, 1996, Induction of mania with serotonin reuptake inhibitors, J. Clin. Psychopharmacol., 16, 425, 10.1097/00004714-199612000-00003 Jensen, 1999, Psychoactive medication prescribing practices for U.S. children: Gaps between research and clinical practice, J. Am. Acad. Child Adolesc. Psychiatry, 38, 557, 10.1097/00004583-199905000-00017 Judd, 2002, The long‐term natural history of the weekly symptomatic status of bipolar I disorder, Arch. Gen. Psychiatry, 59, 530, 10.1001/archpsyc.59.6.530 Jureidini, 2004, Efficacy and safety of antidepressants for children and adolescents, BMJ, 328, 879, 10.1136/bmj.328.7444.879 Kat, 1996, More on SSRI‐induced mania, J. Am. Acad. Child Adolesc. Psychiatry, 35, 975, 10.1097/00004583-199608000-00005 Keller, 1998, Maintenance phase efficacy of sertraline for chronic depression: A randomized controlled trial, JAMA, 280, 1665, 10.1001/jama.280.19.1665 Keller, 1992, Time to recovery, chronicity, and levels of psychopathology in major depression. A 5‐year prospective follow‐up of 431 subjects, Arch. Gen. Psychiatry, 49, 809, 10.1001/archpsyc.1992.01820100053010 Keller, 2001, Efficacy of paroxetine in the treatment of adolescent major depression: A randomized, controlled trial, J. Am. Acad. Child Adolesc. Psychiatry, 40, 762, 10.1097/00004583-200107000-00010 Kelsoe, 1998, Promoter prognostication: The serotonin transporter gene and antidepressant response, Mol. Psychiatry, 3, 475, 10.1038/sj.mp.4000461 Kendler, 2001, Genetic risk, number of previous depressive episodes, and stressful life events in predicting onset of major depression, Am. J. Psychiatry, 158, 582, 10.1176/appi.ajp.158.4.582 Kessler, 1994, Lifetime and 12‐month prevalence of DSM‐III‐R psychiatric disorders in the United States. Results from the National Comorbidity Survey, Arch. Gen. Psychiatry, 51, 8, 10.1001/archpsyc.1994.03950010008002 Kline, 1958, Clinical experience with iproniazid (marsilid), J. Clin. Exp. Psychopathol., 19, 72 Kukopulos, 1983, Rapid cyclers, temperament, and antidepressants, Compr. Psychiatry, 24, 249, 10.1016/0010-440X(83)90076-7 Leverich, 2001, The Stanley Foundation Bipolar Treatment Outcome Network. I. Longitudinal methodology, J. Affect. Disord., 67, 33, 10.1016/S0165-0327(01)00430-X Lewin, 2000 Liebowitz, 2002, Fluoxetine in children and adolescents with OCD: A placebo‐controlled trial, J. Am. Acad. Child Adolesc. Psychiatry, 41, 1431, 10.1097/00004583-200212000-00014 Lucey, 1992, Cortisol and prolactin responses to d‐fenfluramine in non‐depressed patients with obsessive‐compulsive disorder: A comparison with depressed and healthy controls, Br. J. Psychiatry, 161, 517, 10.1192/bjp.161.4.517 Maj, 2002, The prognostic significance of “switching” in patients with bipolar disorder: A 10‐year prospective follow‐up study, Am. J. Psychiatry, 159, 1711, 10.1176/appi.ajp.159.10.1711 Mann, 1983, Loss of antidepressant effect with long‐term monoamine oxidase inhibitor treatment without loss of monoamine oxidase inhibition, J. Clin. Psychopharmacol., 3, 363, 10.1097/00004714-198312000-00007 March, 2004, Fluoxetine, cognitive‐behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial, JAMA, 292, 807, 10.1001/jama.292.7.807 March, 1998, Sertraline in children and adolescents with obsessive‐compulsive disorder: A multicenter randomized controlled trial, JAMA, 280, 1752, 10.1001/jama.280.20.1752 March, 2004, The Child and Adolescent Psychiatry Trials Network (CAPTN), J. Am. Acad. Child. Adolesc. Psychiatry, 43, 515, 10.1097/00004583-200405000-00004 Martin, 2005, In Reply, Arch Ped Adolesc. Med., 159, 298, 10.1001/archpedi.159.3.298-b Martin, 2004, Age effects on antidepressant‐induced manic conversion, Arch. Pediatr. Adolesc. Med., 158, 773, 10.1001/archpedi.158.8.773 McClellan, 1997, Practice parameters for the assessment and treatment of children and adolescents with bipolar disorder, J. Am. Acad. Child. Adolesc. Psychiatry, 36, 157S, 10.1097/00004583-199701000-00032 McGrath, 1993, Paradoxical mood shifts to euthymia or hypomania upon withdrawal of antidepressant agents, J. Clin. Psychopharmacol., 13, 224 Mirin, 1981, Hypomania and mania after withdrawal of tricyclic antidepressants, Am. J. Psychiatry, 138, 87, 10.1176/ajp.138.1.87 Mueller, 1999, Recurrence after recovery from major depressive disorder during 15 years of observational follow‐up, Am. J. Psychiatry, 156, 1000 Mundo, 2001, The role of serotonin transporter protein gene in antidepressant‐induced mania in bipolar disorder: Preliminary findings, Arch. Gen. Psychiatry, 58, 539, 10.1001/archpsyc.58.6.539 Nasrallah, 1982, TCA‐induced mania: Differences between switchers and nonswitchers, Biol. Psychiatry, 17, 271 Nestler, 2004, Cellular and molecular mechanisms of drug addiction, 698 Norrholm, 2000, Chronic fluoxetine administration to juvenile rats prevents age‐associated dendritic spine proliferation in hippocampus, Brain Res., 883, 205, 10.1016/S0006-8993(00)02909-7 Oller, 2003, The 5′‐HTTLPR polymorphism in the SCL6A4 is associated with antideprsesant induced mania in bipolar disorder. Peters, 1976 Post, 1992, Transduction of psychosocial stress into the neurobiology of recurrent affective disorder, Am. J. Psychiatry, 149, 999, 10.1176/ajp.149.8.999 Post, 1997, Drug‐induced switching in bipolar disorder; epidemiology and therapeutic implications, CNS Drugs, 8, 351, 10.2165/00023210-199708050-00002 Post, 2003, A re‐evaluation of the role of antidepressants in the treatment of bipolar depression: Data from the Stanley Foundation Bipolar Network, Bipolar Disord., 5, 396, 10.1046/j.1399-5618.2003.00065.x Post, 1986, Conditioning and sensitisation in the longitudinal course of affective illness, Br. J. Psychiatry, 149, 191, 10.1192/bjp.149.2.191 Post, 1989, Sensitization, kindling, and anticonvulsants in mania, J. Clin. Psychiatry, 50, 23 Pravin, 2004, Citalopram and mania, J. Am. Acad. Child. Adolesc. Psychiatry, 43, 791, 10.1097/01.chi.0000128831.13997.e3 Prien, 1973, Lithium carbonate and imipramine in prevention of affective episodes. A comparison in recurrent affective illness, Arch. Gen. Psychiatry, 29, 420, 10.1001/archpsyc.1973.04200030104017 Prien, 1984, Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate‐imipramine combination, Arch. Gen. Psychiatry, 41, 1096, 10.1001/archpsyc.1983.01790220086014 Quitkin, 1981, Prophylactic lithium carbonate with and without imipramine for bipolar 1 patients. A double‐blind study, Arch. Gen. Psychiatry, 38, 902, 10.1001/archpsyc.1981.01780330060006 Regier, 1993, The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1‐year prevalence rates of disorders and services, Arch. Gen. Psychiatry, 50, 85, 10.1001/archpsyc.1993.01820140007001 Reichart, 2004, Earlier onset of bipolar disorder in children by antidepressants or stimulants? An hypothesis, J. Affect. Disord., 78, 81, 10.1016/S0165-0327(02)00180-5 Reimherr, 1998, Optimal length of continuation therapy in depression: A prospective assessment during long‐term fluoxetine treatment, Am. J. Psychiatry, 155, 1247, 10.1176/ajp.155.9.1247 Rouillon, 1992, Unwanted effects of long term treatment Rousseva, 2003, Antidepressant‐induced mania, rapid cycling and the serotonin transporter gene polymorphism, Pharmacogenomics J., 3, 101, 10.1038/sj.tpj.6500156 Sachs, 1994, A double‐blind trial of bupropion versus desipramine for bipolar depression, J. Clin. Psychiatry, 55, 391 Safer, 1996, Increased methylphenidate usage for attention deficit disorder in the 1990s, Pediatrics, 98, 1084 Schirm, 2001, Psychotropic medication in children: A study from the Netherlands, Pediatrics, 108, E25, 10.1542/peds.108.2.e25 Schmidt, 2002, Treatment approaches to major depressive disorder relapse. Part 1: Dose increase, Psychother. Psychosom., 71, 190, 10.1159/000063643 Sharma, 1998, Venlafaxine: Loss of antidepressant effect and its management, J. Clin. Psychiatry, 59, 381, 10.4088/JCP.v59n0707b Sharma, 2001, Loss of response to antidepressants and subsequent refractoriness: Diagnostic issues in a retrospective case series, J. Affect. Disord., 64, 99, 10.1016/S0165-0327(00)00212-3 Smeraldi, 1998, Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine, Mol. Psychiatry, 3, 508, 10.1038/sj.mp.4000425 Soutullo, 2002, Severity of bipolarity in hospitalized manic adolescents with history of stimulant or antidepressant treatment, J. Affect. Disord., 70, 323, 10.1016/S0165-0327(01)00336-6 Stoll, 1994, Antidepressant‐associated mania: A controlled comparison with spontaneous mania, Am. J. Psychiatry, 151, 1642, 10.1176/ajp.151.11.1642 Strober, 1982, Bipolar illness in adolescents with major depression: Clinical, genetic, and psychopharmacologic predictors in a three‐ to four‐year prospective follow‐up investigation, Arch. Gen. Psychiatry, 39, 549, 10.1001/archpsyc.1982.04290050029007 Verhulst, 1997, The prevalence of DSM‐III‐R diagnoses in a national sample of Dutch adolescents, Arch. Gen. Psychiatry, 54, 329, 10.1001/archpsyc.1997.01830160049008 Versiani, 1999, Reboxetine, a unique selective NRI, prevents relapse and recurrence in long‐term treatment of major depressive disorder, J. Clin. Psychiatry, 60, 400, 10.4088/JCP.v60n0610 Wagner, 2003, Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: Two randomized controlled trials, JAMA, 290, 1033, 10.1001/jama.290.8.1033 Wagner, 2004, A randomized, placebo‐controlled trial of citalopram for the treatment of major depression in children and adolescents, Am. J. Psychiatry, 161, 1079, 10.1176/appi.ajp.161.6.1079 Walkup, 2002, Treatment of pediatric anxiety disorders: An open‐label extension of the research units on pediatric psychopharmacology anxiety study, J. Child Adolesc. Psychopharmacol., 12, 175, 10.1089/104454602760386879 Walkup, 2001, Fluvoxamine for the treatment of anxiey disorders in children and adolescents, N. Engl. J. Med., 344, 1279, 10.1056/NEJM200104263441703 Wegerer, 1999, Persistently increased density of serotonin transporters in the frontal cortex of rats treated with fluoxetine during early juvenile life, J. Child Adolesc. Psychopharmacol., 9, 13, 10.1089/cap.1999.9.13 Wehr, 1979, Rapid cycling in manic‐depressives induced by tricyclic antidepressants, Arch. Gen. Psychiatry, 36, 555, 10.1001/archpsyc.1979.01780050065007 Wehr, 1988, Rapid cycling affective disorder: Contributing factors and treatment responses in 51 patients, Am. J. Psychiatry, 145, 179, 10.1176/ajp.145.2.179 Wilens, 2003, A systematic chart review of the nature of psychiatric adverse events in children and adolescents treated with selective serotonin reuptake inhibitors, J. Child Adolesc. Psychopharmacol., 13, 143, 10.1089/104454603322163862 Wozniak, 1995, Mania‐like symptoms suggestive of childhood‐onset bipolar disorder in clinically referred children, J. Am. Acad. Child Adolesc. Psychiatry, 34, 867, 10.1097/00004583-199507000-00010 Wyeth, 2003 Zajecka, 1997, Discontinuation symptoms after treatment with serotonin reuptake inhibitors: A literature review, J. Clin. Psychiatry, 58, 291, 10.4088/JCP.v58n0702 Garlow, 2004, The neurochemistry of depressive disorders: Clinical stydy, 440