Case of Neutropenia: Depakote vs Quetiapine vs Combination ?

Case of Neutropenia: Depakote vs Quetiapine vs Combination ?

Patient in early 40s African American male with history of mild mental retardation.
Diagnosis of Mood disorder Non Otherwise Specified.

Most recent psychiatric hospitalization 1 year ago for angry outburst and threatening behavior to kill others in residential facility. He was started on Depakote 500 mg BID and Quetiapine titrated to 100 mg HS during this hospitalization. on discharge pt was cooperative, pleasant with no behavioral complaints. He is following at outpatient clinic since then.

No prior psychiatry history is available from residential facility.

Lab work since last 1 year:

Labs ---- Results (Time)
WBC ---- 6 (1 year ago)--- 3.1 (6 m ago)-- 3.8 ( 4 m ago)-- 3.5 (2 m ago)-- 3.5 (2 wk ago)
ANC ----- 3 (1 year ago)--- 1.1 (6 m ago)-- 1.7 ( 4 m ago)-- 1.1 (2 m ago)-- 1.2 (2 wk ago)
Depakote -- 64 (1 year ago)-- X (6 m ago)-- 45 ( 4 m ago)-- X (2 m ago)-- 42 (2 wk ago)
Ammonia --- X (1 year ago)-- 21 (6 m ago)-- 76 ( 4 m ago)-- X (2 m ago)-- X (2 wk ago)

Other labs done 1 year, 6 months and 2 weeks ago are normal: LFTs, TSH and Basic metabolic panel.

I saw this patient for first time 2 weeks ago (transferred patient from other provider).

Since discharge from hospital 1 year ago, no complaints of agitation, confusion, depression, mania, psychosis, signs of infections or other physical manifestation of neutropenia.

I had two options:
(a) To decrease Depakote dose for risk of Depakote induced neutropenia: but his Depakote level is already running low now.
(b) To decrease Quetiapine dose: I opted for this option and decreased Quetiapine to 75 mg PO HS. Reason being Depakote comedication with Quetiapine was observed to have a 77% increase in quetiapine plasma level because of the inhibiting effect on cytochrome P450 3A4.  
Source: Aichhorn W, Marksteiner J, Walch T, et al.. Influence of age, gender, body weight and valproate comedication of quetiapine plasma concentrations. Int Clin Psychopharmacol. 2006; 21: 81–85.  

Please post your inputs and suggestion on this case.

What are the guidelines for medications (Depakote or Quetiapine) discontinuation based on WBC and ANC?
Thanks.

Interesting case. The ANC is getting pretty low.  I would think valproic acid, due to its inhibition of granulocyte-stimulating factor, would be the likely culprit, more so than quetiapine. Although I believe all antipsychotics have a very small chance of agranulocytosis. Given that the ANC is so low though, I would just stop both of them. He seems to have been stable for one year so it wouldn't be far fetched to discontinue them anyway, although I would elect to taper slowly in normal circumstances.

I would use the clozapine guidelines to manage this. Based on his ANC of 1200, he would be classified as moderate agranulocytosis and the recommendation is for interruption of therapy (discontinuation) with daily ANC until ANC >1500, and twice weekly if ANC >2000. You can rechallenge later if the ANC goes over 2000.

It could be possible that this has nothing to do with either medication, although the temporal correlation makes them rather suspect. If the medications are discontinued and there is no change in ANC, I would go ahead and send him to a hematologist. If he has any signs of infection, I would send him to the ED (via making this known to his residential facility's staff).

http://www.clozapineregistry.com/resuming_treatment_after_interruption.pdf.ashx

Thanks P450.

Excellent reply and reference, as always