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<p class="ltrs-br-ltr-br-title">Sertraline and Low-Dose Doxepin Treatment in Severe Agitated-Anxious Depression With Significant Gastrointestinal Complaints: Two Case Reports</p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold">To the Editor</span>: 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.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold-italic">Case 1.</span> 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 <span class="italic">DSM-IV-TR</span> 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. </p>
<p class="ltrs-br-ltr-br-body-text">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.</p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold-italic">Case 2.</span> 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 <span class="italic">DSM-IV-TR</span> 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. </p>
<p class="ltrs-br-ltr-br-body-text">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.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text">Symptoms of anxiety and agitation are common among depressed patients and are predictive of poor response to antidepressants.<span class="htm-cite"><a href="#ref1">1</a>,<a href="#ref2">2</a></span> Additionally, GI symptoms are often associated with these conditions.<span class="htm-cite"><a href="#ref3">3–5</a></span> 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.<span class="htm-cite"><a href="#ref6">6–8</a></span> The use of sertraline and low-dose doxepin has shown initial treatment success in these 2 cases.</p>
<p class="ltrs-br-ltr-br-references-head"><span class="smallcaps">References</span></p>
<p class="references-references-text-1-9"><a name="ref1"></a>1. Olgiati P, Serretti A, Colombo C. Retrospective analysis of psychomotor agitation, hypomanic symptoms, and suicidal ideation in unipolar depression. <span class="italic">Depress Anxiety</span>. 2006;23(7):389–397. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16823857&dopt=Abstract">PubMed</a> <a href="
http://dx.doi.org/10.1002/da.20191">doi:10.1002/da.20191</a></span></p>
<p class="references-references-text-1-9"><a name="ref2"></a>2. Hamilton M. Distinguishing between anxiety and depressive disorders. In: Last SCA, Hersen M, eds. <span class="italic">Handbook of Anxiety Disorders</span>. New York, NY: Pergamon Press; 1988:143–145.</p>
<p class="references-references-text-1-9"><a name="ref3"></a>3. North CS, Hong BA, Alpers DH. Relationship of functional gastrointestinal disorders and psychiatric disorders: implications for treatment. <span class="italic">World J Gastroenterol</span>. 2007;13(14):2020–2027. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17465442&dopt=Abstract">PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref4"></a>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. <span class="italic">Int J Clin Pract</span>. 2008;62(7):1063–1069. <span class="pubmed-crossref"><a href="
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http://dx.doi.org/10.1111/j.1742-1241.2008.01763.x">doi:10.1111/j.1742-1241.2008.01763.x</a></span></p>
<p class="references-references-text-1-9"><a name="ref5"></a>5. Lydiard RB, Falsetti SA. Experience with anxiety and depression treatment studies: implications for designing irritable bowel syndrome clinical trials. <span class="italic">Am J Med</span>. 1999;107(5A):65S–73S. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10588175&dopt=Abstract">PubMed</a> <a href="
http://dx.doi.org/10.1016/S0002-9343(99)00082-0">doi:10.1016/S0002-9343(99)00082-0</a></span></p>
<p class="references-references-text-1-9"><a name="ref6"></a>6. Dunbar GC, Fuell DL. The anti-anxiety and anti-agitation effects of paroxetine in depressed patients. <span class="italic">Int Clin Psychopharmacol</span>. 1992;6(suppl 4):81–90. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1431016&dopt=Abstract">PubMed</a> <a href="
http://dx.doi.org/10.1097/00004850-199206004-00014">doi:10.1097/00004850-199206004-00014</a></span></p>
<p class="references-references-text-1-9"><a name="ref7"></a>7. Jackson JL, O’Malley PG, Tomkins G, et al. Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. <span class="italic">Am J Med</span>. 2000;108(1):65–72. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11059442&dopt=Abstract">PubMed</a> <a href="
http://dx.doi.org/10.1016/S0002-9343(99)00299-5">doi:10.1016/S0002-9343(99)00299-5</a></span></p>
<p class="references-references-text-1-9"><a name="ref8"></a>8. Vij JG, Jiloha RC, Kumar N, et al. Effect of antidepressant drug (doxepin) on irritable bowel syndrome patients. <span class="italic">Indian J Psychiatry</span>. 1991;33:243–246.</p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Lisa MacLean, MD</span></p>
<p class="ltrs-br-ltr-br-author"><a href="
mailto:lmaclea1@hfhs.org" target="_blank">
lmaclea1@hfhs.org</a></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Brian K. Ahmedani, PhD</span></p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Author affiliations:</span> Henry Ford Health System, Detroit, Michigan.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Potential conflicts of interest: </span>None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Funding/support: </span>None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Published online:</span> August 4, 2011 (<span class="doi">doi:10.4088/PCC.11l01152</span>).</p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">Prim Care Companion CNS Disord 2011;13(4):</span><span class="doi">doi:10.4088/PCC.11l01152</span></p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">© Copyright 2011 Physicians Postgraduate Press, Inc.</span></p>
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