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Letter to the Editor

Sertraline and Low-Dose Doxepin Treatment in Severe Agitated-Anxious Depression With Significant Gastrointestinal Complaints: Two Case Reports

Lisa MacLean, MD and Brian K. Ahmedani, PhD

Published: August 4, 2011

Sertraline and Low-Dose Doxepin Treatment in Severe Agitated-Anxious Depression With Significant Gastrointestinal Complaints: Two Case Reports

To the Editor: Selective serotonin reuptake inhibitors (SSRIs) have shown efficacy in the treatment of agitated-anxious depression. Nonetheless, they can exacerbate both anxiety and stomach complaints among patients with significant gastrointestinal (GI) symptoms. We report on the treatment of 2 cases of agitated-anxious depression with corresponding GI problems.

Case 1. Ms A, a 53-year-old female patient suffering from agitation, recurrent severe depression, rumination, excessive worry, severe GI symptoms, and marked distress, fulfilled the DSM-IV-TR criteria for major depressive disorder, recurrent, severe, without psychosis as well as generalized anxiety disorder in 2008. During a 6-month period prior to the intervention, she was prescribed alprazolam; an elixir of atropine sulfate, hyoscyamine sulfate, phenobarbital, and scopolamine hydrobromide; famotidine; prochlorperazine; citalopram; fluoxetine; nefazodone; paroxetine; clonazepam; and escitalopram without success. The patient reported intolerability to the antidepressants, sedation associated with the benzodiazepines, recurring GI problems, and hopelessness regarding future treatment.

At the current presentation, she was initially placed on treatment with sertraline (12.5 mg daily) with low-dose diazepam (2 mg up to 3 times daily). After 2 weeks, doxepin (25 mg/d) was added to address considerable GI distress and poor sleep. At this point, sertraline was also increased to 25 mg daily and was subsequently increased 25 mg every 2 weeks until a 100-mg daily dose was reached at 8 weeks. The use of diazepam was reduced in parallel and was discontinued at 14 weeks. The slow titration process occurred due to concerns regarding tolerability. Throughout the early titration, the patient complained of considerable distress, anxiety, depression, and frustration. GI distress began to lessen within 2 weeks of doxepin initiation, and by 12 weeks the patient was in full remission from anxiety and depression without any GI side effects. The patient has been maintained on treatment with sertraline (100 mg/d) and doxepin (25 mg/d) for 6 years without relapse.

Case 2. Mr B, a 56-year-old male patient suffering from gradual onset of severe anxiety, depression, insomnia, rumination, worry, severe GI symptoms, and marked distress fulfilled the DSM-IV-TR criteria for major depressive disorder, single episode, severe without psychosis as well as generalized anxiety disorder in 2010. During a 10-week period prior to his initial consultation, Mr B had been prescribed combinations of amitriptyline, paroxetine, bupropion, lorazepam, alprazolam, mirtazapine, quetiapine, buspirone, escitalopram, aripiprazole, zolpidem, and triazolam. The patient either had no response or experienced intolerable side effects to these treatments. At presentation, his target symptoms were insomnia, GI symptoms, and hopelessness regarding treatment.

At the current presentation, the patient was initially started on treatment with doxepin (10 mg) and clonazepam (1 mg) if needed at bedtime. After 1 week, the clonazepam was replaced with lorazepam (1-2 mg). At week 2, doxepin was increased to 20 mg/d, while sertraline (12.5 mg/d) and trazodone (50 mg/d) were added. Sertraline was then increased to 25 mg/d and subsequently increased 25 mg weekly until a 100-mg daily dose was reached at week 8. Trazodone was also increased (150 mg/d), while lorazepam was limited to 1 bedtime dose (1 mg), which was subsequently discontinued by the patient. The patient was in full remission by week 11 and returned to work as a physician. The patient continues on treatment with sertraline (100 mg), doxepin (20 mg), and trazodone (150 mg) at bedtime and has been in full remission for 3 consecutive months.

Symptoms of anxiety and agitation are common among depressed patients and are predictive of poor response to antidepressants.1,2 Additionally, GI symptoms are often associated with these conditions.3-5 While SSRIs can be used to successfully treat agitated depression, and tricyclic antidepressants, including doxepin, have been used to treat GI problems, patients may present with these problems simultaneously.6-8 The use of sertraline and low-dose doxepin has shown initial treatment success in these 2 cases.


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2. Hamilton M. Distinguishing between anxiety and depressive disorders. In: Last SCA, Hersen M, eds. Handbook of Anxiety Disorders. New York, NY: Pergamon Press; 1988:143-145.

3. North CS, Hong BA, Alpers DH. Relationship of functional gastrointestinal disorders and psychiatric disorders: implications for treatment. World J Gastroenterol. 2007;13(14):2020-2027. PubMed

4. Addolorato G, Mirijello A, D’ Angelo C, et al. State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting. Int J Clin Pract. 2008;62(7):1063-1069. PubMed doi:10.1111/j.1742-1241.2008.01763.x

5. Lydiard RB, Falsetti SA. Experience with anxiety and depression treatment studies: implications for designing irritable bowel syndrome clinical trials. Am J Med. 1999;107(5A):65S-73S. PubMed doi:10.1016/S0002-9343(99)00082-0

6. Dunbar GC, Fuell DL. The anti-anxiety and anti-agitation effects of paroxetine in depressed patients. Int Clin Psychopharmacol. 1992;6(suppl 4):81-90. PubMed doi:10.1097/00004850-199206004-00014

7. Jackson JL, O’ Malley PG, Tomkins G, et al. Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med. 2000;108(1):65-72. PubMed doi:10.1016/S0002-9343(99)00299-5

8. Vij JG, Jiloha RC, Kumar N, et al. Effect of antidepressant drug (doxepin) on irritable bowel syndrome patients. Indian J Psychiatry. 1991;33:243-246.

Lisa MacLean, MD

Brian K. Ahmedani, PhD

Author affiliations: Henry Ford Health System, Detroit, Michigan.

Potential conflicts of interest: None reported.

Funding/support: None reported.

Published online: August 4, 2011 (doi:10.4088/PCC.11l01152).

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