Citalopram in Child and Adolescent Depression With Anxiety
October 31, 2001
James L. Schaller, MD, David Behar, MD
Medscape General Medicine 3(4), 2001.
The paucity of selective serotonin reuptake inhibitor (SSRI) studies in child and adolescent psychiatry represents a serious frustration for clinicians treating youth with major depression (MD). We report 4 cases illustrating citalopram's low rate of anxiety symptoms or low "activation," an important consideration in medication choice. Youth may resist further medication treatment if they experience iatrogenic activation or increased anxiety.
Citalopram has been in use outside the United States since 1989, is approved for use in 69 countries, and is the most selective SSRI.[1,2] In terms of anxiety side effects, citalopram demonstrated less need for concomitant anxiolytics/hypnotics vs fluoxetine in average doses. Citalopram had a low rate of activation (only a 0.4% to 1.4% increase above placebo on 4 separate anxiety measures), along with strong anxiolytic effects in adults.[5,6] In contrast to less selective SSRIs, it has not been reported to produce the dysphoria of akathisia.[7-15] Further, citalopram resulted in better patient compliance during initiation of treatment compared with sertraline, with superior anxiolytic benefit. Citalopram treatment of youth anxiety demonstrates an antianxiety benefit with minimal activation/anxiety on initiation.[17-20] Yet, currently, there are no child or adolescent head-to-head SSRI anxiety studies in children. This case series is meant to raise the question: do all SSRIs share the same rates of initial anxiety and activation side effects?
A 12-year-old boy meeting DSM IV-TR criteria for MD with suicidal ideation, with a suicide plan and minimal suicidal intent, was started on 20 mg of fluoxetine by his pediatrician. For 2 days, he averaged 6 hours of sleep per day — a decrease from 9 hours a day. He appeared unsettled and "more nervous" according to his family (eg, with new biting of both fingernails and even his toenails). He was no longer able to calmly watch television.
His fluoxetine was immediately replaced with 10 mg of citalopram at breakfast — on day 3. Both he and his family reported a decrease in his "nervousness" the day of his first dose. For example, he was now able to sit calmly, watch television, and stopped biting his nails. Due to his continuing suicidal symptoms, along with the unexpected relief of anxiety/activation side effects, he was tried on an additional 10 mg of citalopram that same evening (treatment day 3) with no return of nervousness, nail biting, or insomnia. He was continued on 20 mg of citalopram daily. He had a gradual yet full remission of his depression over 2 months, with no further anxiety or activation side effects.
The sudden decrease in anxiety after only 1 dose change was unexpected. Possible etiologies include: citalopram is less activating than fluoxetine, the 2 SSRIs have different potencies at similar doses, or the youth suddenly developed tolerance to SSRI-induced anxiety. Regarding this latter hypothesis, while resolution of significant SSRI anxiety is common, resolution occurring so quickly and completely is clinically noteworthy.
A 15-year-old female with MD and panic disorder was placed on paroxetine 10 mg for 5 days, then 20 mg. She reported an abrupt increase in suicidal ideation, new marked anxiety and insomnia, and dysphoric sedation within 24 hours of her paroxetine increase. Her Beck Anxiety Scale (BAI) rose from a 13 before treatment to a 23 on paroxetine 20 mg. She was converted to citalopram 10 mg with a prompt "75%" decrease in sedation and a marked decrease in her anxiety (BAI of only 5). At 48 hours, she was increased to 20 mg of citalopram, with no increase in anxiety or insomnia. Six days later, she was increased to 30 mg and only reported a decrease in appetite but no anxiety, insomnia, or sedation. At 4 weeks, she no longer met DSM IV-TR criteria for MD or panic disorder.
The patient apparently experienced marked iatrogenic anxiety with a paroxetine dose increase from 10 mg to 20 mg. And yet she was fully able to tolerate 20 mg of citalopram within 48 hours. While it is possible she habituated to SSRI anxiety side effects, such a prompt decrease of anxiety in 48 hours may be more than mere side effect habituation.
A 17-year-old female meeting DSM IV-TR criteria for MD was started by her adult psychiatrist on 20 mg of fluoxetine. After her first dose, she had profound agitation and panic attacks and went to an emergency room because she felt she "was going crazy." She was medically cleared of any nonpsychiatric causes of the panic attacks and treated with lorazapam 2 mg, and 5 hours later another 1 mg. Her panic and dysphoria resolved. After 36 hours, the patient was prescribed 10 mg of citalopram but took 20 mg without a return of her agitation or panic attacks.
This patient had severe panic attacks on 20 mg of fluoxetine and it was promptly stopped. On citalopram 20 mg she had no agitation, anxiety, or panic. These 2 trials were separated by 1.5 days. It appears unlikely that the patient could have habituated to profound panic in such a short time after marked side effects from the initial trial.
An 18-year-old female was stable on citalopram according to retrospectively administered MD and anxiety scales. Her internist changed her medication to paroxetine 20 mg because it was "better for anxiety." She was changed abruptly in 24 hours. She had new onset insomnia, vivid "bad dreams," and panic attacks (3-5 per day in week 1). The patient cut her dose to 10 mg for a week with improved sleep and reduced panic attacks (once daily). Her internist believed that her paroxetine was underdosed, and increased her paroxetine to 20 mg for 1 dose. The patient had 6 panic attacks in 24 hours. Finally, the patient was returned to citalopram 20 mg. Her "anxiety" seemed to be reasonable "concerns" about college, so she received no dose increase or antianxiety agent. Her panic attacks fully resolved in a week without cognitive-behavioral treatments or benzodiazepines.
In this case, citalopram is the initial baseline medication. A shift to paroxetine caused a clear increase in insomnia and panic attacks. Returning this adolescent female to her citalopram brought about an abrupt end of her sleep and panic symptoms.
We propose that these clinical case reports show that citalopram may be an appropriate treatment for child and adolescent depression, particularly if an anxiety component is present. At their recommended doses, our small case series found that citalopram was better tolerated than other common SSRIs in patients reporting anxiety and panic attacks. We propose SSRIs may vary in terms of their anxiety side effects in this age group. Also, citalopram's tolerability in anxious patients might be due to potency variations. Specifically, clinical assumptions about comparable potency (eg, that paroxetine 20 mg is similar in potency to citalopram 20 mg) may be incorrect.
The question of SSRI activation requires further large-scale, double blind, clinical trials for a definitive answer. Studies should pair SSRIs of established comparable potency and note any differences in activation and anxiety. Such trials should be done in children and adolescents.
Finally, the relative lack of anxiety onset side effects for citalopram in these cases does not mean starting doses nor increases should be overly aggressive.—
James L. Schaller, MD, is a paid speaker for Forest Pharmaceuticals, the makers of Celexa.
James L. Schaller, MD, President, Chester County Research Center, Chester Springs, Pennsylvania. E-mail: JLSCHALLER@aol.com. David Behar, MD, Clinical Assistant Professor, Eastern Pennsylvania Psychiatric Institute, Philadelphia, Pennsylvania.