TESTING: CT FINDINGS
Approximately 2 months after admission—shortly after a blood draw shows normal WBC and neutrophils—Mr. G complains of dizziness. He says he accidentally hit his head against a side table.

We order a full neurologic workup to check for traumatic brain injury or brain damage caused by long-term alcohol abuse:
• Head CT shows evidence of previous cerebrovascular infarcts in the bilateral frontal and cerebellar lobes and basal ganglia.
• MRI shows atrophied mammillary bodies, fornix, and corpus callosum.
• Magnetic resonance angiography reveals small cerebral vessel disease.
These findings and subsequent neuropsychiatric test results suggest an organic cause of depression, likely secondary to 12 years of alcohol abuse. In light of this new information, we change Mr. G’s diagnosis to mood disorder with depressive features secondary to a general medical condition.

FOLLOW-UP: AWAITING DISCHARGE
After 3 months of continuous hospitalization, Mr. G has become euthymic and nonsuicidal, though at times oversensitive and combative. We transfer him to an assisted-living center and continue sertraline, 150 mg/d; phenytoin, 300 mg/d; phenobarbital, 30 mg bid; lithium, 300 mg/d; and trazodone, 50 mg at night as needed for insomnia.

We also place Mr. G in a day treatment program for mentally ill chemical abusers. A psychiatrist sees him every 2 weeks, and staff supervise him daily.

When starting sertraline or bupropion, order blood tests:
__ at baseline and every 2 weeks
__ at baseline and every 4 weeks
__ 1 month after starting and every 6 months thereafter
__ would not order unless patient shows physical symptoms

The authors’ observations
Mr. G’s extended hospital stay allowed us to closely observe him and offered ready access to laboratory facilities while we cross-tapered medications. In outpatient treatment, however, a serious and life-threatening medication-induced complication could easily be missed.

If economically feasible, take CBCs for all patients before prescribing any medication that could cause neutropenia, such as an antidepressant or mood stabilizer. Make sure geriatric or medically ill patients have had a CBC ≤3 months before presentation and are seeing a primary care physician as needed. Order follow-up CBC for these patients 1 month after presentation, then every 6 months if CBC is normal.

For medically healthy outpatients, be sure CBC has been checked ≤6 months before presentation. Monitor CBC and urge the patient to see a primary care doctor if infection symptoms emerge. Watch for gingivitis, tooth abscess, and other oral cavity infections—which often are overlooked—and sore throat or fever.

Also check electrolytes and screen for SSRI-induced hyponatremia at baseline for all at-risk patients.

Stop the offending drug when WBC reaches <2×109/L or with absolute neutrophil count (ANC) <1.5×109/L, then take a peripheral smear to confirm neutropenia. If the patient is asymptomatic, check ANC 2 to 3 times weekly, particularly if he or she recently had an infection or started a medication that can cause neutropenia. Neutropenia should resolve within 6 to 8 weeks of stopping the offending drug.

If neutropenia persists, order bone marrow biopsy in collaboration with an internist or hematologist to test for cancer. If the biopsy is negative, test for:
• HIV infection
• antinuclear antibodies to check for collagen vascular disease
• antineutrophil antibody to rule out immune neutropenia
• serum folate and B12 deficiency secondary to low WBC.

Also perform an immunoglobulins/immune evaluation to check for defects in cellular or humoral immunity, and bone marrow culture to test for infection.8

FOLLOW-UP: STRESSOR AND RELAPSE
Seven months later, Mr. G is readmitted for depression. Three months earlier, he had stopped all medications and resumed drinking after a family member died. WBC at admission is 3.70×109/L.

We restart sertraline, 150 mg/d. WBC falls to 2.83×109/L 12 days later, so we add lithium, 300 mg/d. Two days later, WBC returns to normal and he is discharged. His depression has been stable throughout this second admission, and he is euthymic at discharge.
We refer Mr. G to an outpatient psychiatrist, who sees him monthly. Several months later, the psychiatrist reports a WBC of 4.58×109/L.

Nearly 1 year later, Mr. G still lives at the assisted-living facility. He has not been rehospitalized for depression, is functioning well, and has a girlfriend.

The authors’ observations
Mr. G’s abnormal blood counts after sertraline rechallenge confirms that the SSRI probably was causing leukopenia. If we had restarted bupropion and neutropenia recurred during that regimen, we could have more certainly established a bupropion-leukopenia connection.

Related resources
• Neutropenia Support Association. www.neutropenia.ca.
• Baehner RL. Overview of neutropenia.UpToDate Online (version 15.1); March 30, 2006. www.uptodate.com.

Drug brand names
Bupropion • Wellbutrin
Carbamazepine • Tegretol, others
Citalopram • Celexa
Clozapine • Clozaril
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Lamotrigine • Lamictal
Lithium • various
Mirtazapine • Remeron
Oxcarbazepine • Trileptal
Paroxetine • Paxil
Phenobarbital • various
Phenytoin • Dilantin
Propylthiouracil • various
Sertraline • Zoloft
Trazodone • Desyrel
Valproic acid • Depakene
Venlafaxine • Effexor

Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

References
1. McEvoy G, ed. AHFS drug information. Bethesda, MD: American Society of Health-System Pharmacists; 2005.

2. Nelson JC. Safety and tolerability of the new antidepressants. J Clin Psychiatry 1997;60:1101.

3. Physicians desk reference, 61st ed. Montvale, NJ: Thomson PDR; 2007.

4. Cohn CK, Shrivastava R, Mendels J, et al. Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. J Clin Psychiatry 1990;51(suppl B):28–33.

5. Trescoli-Serrano C, Smith NK. Sertraline-induced agranulocytosis. Postgrad Med J 1996;72:446.

6. Baehner RL. Overview of neutropenia.UpToDate Online (version 15.1); March 30, 2006. Available at: http://www.uptodate.com. Accessed April 16, 2007.

7. Lima CS, Paula EV, Takahashi T, et al. Causes of incidental neutropenia in adulthood. Ann Hematol 2006;85:705–9.

8. Holland SM, Gallin J. Disorders of granulocytes and monocytes. In: Kasper DL, Braunwald E, Fauci AS, et al, eds. Harrison’s principles of internal medicine, 16th ed. New York: McGraw-Hill; 2005.

9. Baehner RL. Drug-induced neutropenia and agranulocytosis.UpToDate Online (version 15.1); June 8, 2005. Available at: http://www.uptodate.com. Accessed April 16, 2007.

10. Sporn A, Gogtay N, Ortiz-Aguayo R, et al. Clozapine-induced neutropenia in children: management with lithium carbonate. J Child Adolesc Psychopharmacol 2003;13:401–4.

11. Blier P, Slater S, Measham T, et al. Lithium and clozapine-induced neutropenia/agranulocytosis. Int Clin Psychopharmacol 1998;13:137–40.

12. Silverstone P. Prevention of clozapine-induced neutropenia by pretreatment with lithium. J Clin Psychopharmacol 1998;18:86–8.

13. Ozcanli T, Unsalver B, Ozdemir S, Ozmen M. Sertraline and mirtazapine-induced severe neutropenia. Am J Psych 2005;162:1386.

14. Vilinsky FD, Lubin A. Severe neutropenia associated with fluoxetine hydrochloride. Ann Internal Med 1997;127:573–4.


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