in Adolescent Major Depression
Lexapro (Escitalopram) is the purified functional isomer contained in citalopram. Specifically, escitalopram is the S-enantiomer of citalopram. The latter is used worldwide in 89 countries and in approximately 40 million patients. Since first approved in Denmark in 1989, escitalopram has been prescribed in 26 countries.1-3
Currently, in the USA, the only FDA approved selective, serotonin re-uptake inhibiter (SSRI) for adolescents is fluoxetine (Prozac).4 It is preferred if caretakers wish an FDA approved SSRI for their adolescent. Also, fluoxetine typically does not have withdrawal symptoms if a dose is missed. However, this SSRI may not always be functional or optimal. We describe some cases in which escitalopram might be considered a useful alternative.
A 16 y/o female girl with two, mildly obese parents had a Body Mass Index (BMI) of 34 and a 37-inch waist. She was diagnosed with Major Depression (MD) from DSM-IV TR criteria via a clinical interview and by the Inventory to Diagnose Depression (IDD).5 Her symptoms included fatigue, sadness, anhedonia, new restlessness and social anxiety. Paroxetine (Prozac) was started by her behavioral pediatrician in an effort to simultaneously treat her social anxiety and MD. She was started on 5 mg without side effects, but at three weeks she had no MD improvement. She was subsequently increased to 25 mg over three months. She demonstrated a decrease in her MD from an IDD of 36 to 13 (0-10 is normal), but she gained 12-15 pounds.
As a result of her demoralization and frustration, paroxetine (Paxil) was decreased to 10 mg and she was placed on escitalopram 7.5 mg. Her IDD was 11, 14, and 9 spaced over four weeks. She lost 6 pounds in a month. The following month escitalopram was raised up to 20 mg. After the removal of the paroxetine and the addition of the escitalopram she lost an additional 10-12 pounds over two months. It appears that paroxetine may increase weight in some patients, and this probably includes adolescent patients.6
A 15 y/o male with a DSM-IV TR diagnosis of MD reported feeling, "uncomfortable, and miserable" and needing,"to move" daily, after being on fluoxetine 20 mg/day for three weeks. He had no baseline anxiety disorder or anxious cognitions; only new body restlessness. Upon starting the fluoxetine, his discomfort was reported to his pediatrician, who told his mother, "it would go away." When his status remained unchanged over five weeks, the youth was reduced to 10 mg with a partial decrease in his agitation that was still very unacceptable to the boy.
The youth was diagnosed by a child psychiatrist as having fluoxetine-induced akathisia. He was placed on escitalopram 5 mg with subsequent cessation of his agitation and restlessness in two days. He reported "mild" headaches, during his first 36 hours, and escitalopram was increased to 10 mg on day seven. He was increased to 20 mg escitalopram due to residual anhedonia and a sad mood. He had complete remission of his MD in six weeks, with no symptoms of restlessness, akathisia, parkinsonian symptoms, dystonia or bruxism.
We did a literature search of Pubmed, specifically searching each movement disorder mentioned above with common antidepressants. We found extensive studies of SSRI-induced movement disorders associated with fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). 7,8 However, fluvoxamine (Luvox) and escitalopram/citalopram (Lexapro/Celexa) had only a few incidents in the literature. We hypothesize that this is not due to a shortage of studies, since each medication mentioned has thousands of publications in Pubmed. And while Nefazodone (Serzone) and venlafaxine (Effexor) had minimal reports of movement disorders they also had fewer references--nefazodone with 515 references and venlafaxine with 1045 references. Differing recepter affinities may play a role in movement disorder variation.
A 17 y/o female was successfully treated for DSM-IV TR Major Depression for approximately 2 _ years on increasing doses of sertraline. The patient initially had a four-month remission of MD on 75 mg of sertraline. She then required an increase of 37.5 mg over twelve weeks in the winter while residing in the Northeast USA. She was diagnosed as having a seasonal affective disorder (SAD) in addition to her MD. A steady state, ÒpeakÓ blood level was drawn 5-7 hours after am dosing which was 61ng/ml.
The following winter she had a relapse of MD, in the absence of any significant psychosocial stressors, and required 200 mg of sertraline. Her peak steady state level was 174 ng/ml. A year later, she had a sertraline level of 93 ng/ml; and was judged to be having another relapse of MD. (No medications, herbs, or foods could be identified as confounders of sertraline metabolism).
Her family, the treating physician, and the patient were concerned about continuous relapses and possible serum level drift. As a result, she was started at 5 mg of escitalopram in addition to her sertraline 200 mg with full remission. She was weaned to 25 mg of escitalopram, and terminated sertraline over 2 months. She has had no relapse in seven months, and without need for a medication increase. We hypothesize that sertraline has a possible downward serum level drift each year. This drift may allow for a breakthrough in SAD symptoms during the winter months in the Northern USA. It is unclear whether this exists in other SSRIÕs over years in treatment.
A 14 y/o female had migraines, MD and Impulse Disorder NOS by DSM-IV TR criteria. Her mother found various drug interactions with SSRIÕs on the internet. Specifically, she read that risperdal and propranolol, two medications her daughter was currently receiving, could interact with many SSRI options. She asked for the antidepressant with the lowest possible interactions. Since escitalopramÕs preliminary data has markedly low interactions at the CP450 system,9-11 and was also reported to have no discernable interaction with over 125 neurologically relevant ligands, (including receptors associated with common SSRI side effects),12 it was her motherÕs choice for treatment. Her daughter was started on 5 mg at night. After a week escitalopram was raised to 10 mg, and in a month was placed on 15 mg, where she has remained MD free for four months.
A 15 y/o female was diagnosed with Major Depression by DSM-IV TR and was reported to have Borderline personality traits by her psychologist. On intake, her mother and maternal aunt volunteered they both had a good response to citalopram for their own MD. They wanted their genetic experience considered in any medication choice. The mother added she had, "a panic attack on paroxetine" starting at 10 mg; and the aunt also had panic symptoms when started on fluoxetine at 20 mg.
The youth was started on _ of 10 mg escitalopram for two days and then increased to 5 mg. without side effects. In seven days she was raised to 10 mg of escitalopram, and judged to be in full remission three weeks later; her IDD decreased from 28 to 6. Against medical advice, the patient reduced her dose to 5 mg for two days and skipped one dose, since, "it was a foreign chemical." She reported a return of her depressive symptoms, and took 10 mg of her motherÕs old paroxetine. She had a panic attack within hours, yet was able to sooth herself by saying to herself, "This happened to my mom, it will go away."
The mother discarded her own paroxetine, and the patient was restarted on 5 mg escitalopram for two days and then subsequently 10 mg. She remained symptom free of MD. She was rigorously educated on MD, as well as antidepressant functioning, and her psychologist addressed her acting-out with medications. In the last five months the patient has been stable, without any MD. Some literature reports that escitalopram may reduce anxiety at onset.13-14 Such claims seem consistent with this adolescent patientÕs experience.
In conclusion, the various options available to child and adolescent psychiatrists are very diverse and increasing. We should avoid the temptation to view current modern new generation antidepressants as clones, when they have meaningful differences. At least these cases highlight some possible differences that will benefit from additional study.
James L. Schaller, MD, MAR
239 263 0133
David B. Rawlings, Ph.D., PA, ABPN
American Board of Professional Neuropsychology
- Burke WJ (2002), Escitalopram. Expert Opinion 11;1478
- http://www.psychotropics.dk/usr_view_molecule.asp?ID=3790&historyline=&backurl=%2Fdefault%2Easp%3FSearchword%3Dcitalopram%26Searchtype%3DAll&backurlname=Search+Result&Catalogtype=A. Accessed on July 25, 2003
- Lundbeck resources page (2004), H. Lundbeck A/S corporation Web site. Available at: http://www.lundbeck.com/investor/Productsandmarkets/Launchedproducts/Default.asp. Accessed on July 25, 2003
- FDA resources page (2003), Food and Drug Administration Web site. Available at: http://www.fda.gov/fdac/departs/2003/203_upd.html#prozac. Accessed June 13, 2004
- Zimmerman M, Coryell W (1988), The validity of a self-report questionnaire for diagnosing major depressive disorder. Arch Gen Psychiatry 45:738-40
- Bandelow B, Behnke K, Lenoir S, Hendriks GJ, Alkin T, Goebel C, Clary CM (2004), Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. J Clin Psychiatry 65:405-13
- Schaller JL (2003) Studies of movement disorders and SSRIÕs. http://www.personalconsult.com/articles/ssricme1.html. Accessed June 2, 2004.
- Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI (1999), Human cytochromes and some newer antidepressants: kinetics, metabolism, and drug interactions. J Clin Psychopharmacol 19:23S-35S
- von Moltke LL, Greenblatt DJ, Giancarlo GM, Granda BW, Harmatz JS, Shader RI (2001), Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab Dispos 29:1102-9
- Greenblatt DJ, Hesse LM, Giancarlo GM, Harmatz JS, Shader RI (2001), The S-entantiomer of citalopram: cytochromes P450 mediating metabolism and cytochrome inhibitory effects (poster). Presented at the Annual Scientific Convention of the Society of Biological Psychiatry. May 2001, New Orleans, LA
- Sanchez C, Brennum L. Escitalopram is a highly seective and potent serotonin reuptake inhibitor. In vitro studies. Poster presented at the 1st
Annual meeting of the Scandinavian College of Neuropsychopharmacology, April 18-20, 2001, Juan-Les-Pins, France
- Gorman JM, Korotzer A, Su G (2002), Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. CNS Spectr 7:40-4
- Fish EW, Faccidomo S, Gupta S, Miczek KA (2004), Anxiolytic-like effects of escitalopram, citalopram, and R-citalopram in maternally separated mouse pups. J Pharmacol Exp Ther 308:474-80
- Stahl SM, Gergel I, Li D (2003), Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 64:1322-7