Safety and efficacy of combined clozapine–lithium pharmacotherapy

Bender, Stefan; Linka, T.; Wolstein, Jörg; Gehendges, Susanne; Paulus, Hermann-Josef; Schall, Ulrich; Gastpar, Markus

doi:10.1017/s1461145703003870

Cited by 53 publications

(26 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are case reports of adverse neurological effects, including tremors, involuntary movements, and seizures (16,34,36,37), as well as case reports of agranulocytosis (38,39), in patients taking clozapine and lithium. However, the adverse neurological effects reported in most cases were transient and occurred only during initiation of lithium treatment (16,36,40); in other cases, the picture was complicated by polypharmacy and the possible contribution of other medications, including haloperidol (16) and serotonergic agents (40). Similarly, one of the two cases of agranulocytosis reported was complicated by haloperidol, as well as a number of anticonvulsants that themselves carry a risk of blood dyscrasia in that patient's medication regimen (39).…”

Section: Discussionmentioning

confidence: 99%

Rechallenging With Clozapine Following Neutropenia: Treatment Options for Refractory Schizophrenia

Ghaznavi¹,

Nakic²,

Rao³

et al. 2008

AJP

View full text Add to dashboard Cite

Cl ozapine, a second-generation antipsychotic, is the treatment of choice in refractory schizophrenia because of its proven efficacy over typical antipsychotics as well as other atypical antipsychotics (1). However, a major drawback to clozapine therapy is the increased risk of neutropenia and agranulocytosis (2). In patients who develop either of these serious side effects, clozapine is immediately discontinued. Unfortunately, trials of other antipsychotics often prove ineffective, and clinicians find themselves faced with the difficult decision of whether to rechallenge those patients with clozapine (3). Even more concerning for the clinician is the relative absence of any controlled data to suggest treatment options when clozapine cannot be used because of serious side effects, such as neutropenia or agranulocytosis. This case review highlights this particular aspect and provides some useful thinking points for clinicians and patients in this situation.Efforts at rechallenge with clozapine have met with some success (4-9). In a retrospective review of 53 cases of clozapine rechallenge in the United Kingdom and Ireland, 62% of the patients did not develop a blood dyscrasia on rechallenge (8). Of course, clozapine rechallenge is not without its risks. In the same retrospective review, it was found that among the 38% of cases who did develop a blood dyscrasia on rechallenge, in 85% of the cases, the blood dyscrasia occurred more quickly and was more severe than with the initial trial of clozapine. In addition, in 65% of the cases in which patients developed a blood dyscrasia on rechallenge, the blood dyscrasia lasted longer after discontinuation of clozapine following rechallenge than when clozapine was first discontinued. Thus, when deciding whether to rechallenge a patient with clozapine, the clinician must carefully weigh the risks and benefits of a clozapine rechallenge. Here we present a patient with refractory schizophrenia who successfully tolerated a clozapine challenge 2 years after developing clozapine-induced neutropenia and failing to respond to a subsequent clozapine rechallenge. We propose that polypharmacy may have contributed to the initial episode of neutropenia as well as the failed clozapine rechallenge in our patient. We also discuss logical issues in medical decision making before considering clozapine rechallenges in patients.Case Presentation "S.P." was a 55-year-old divorced African American man with a 30-year history of paranoid schizophrenia who was referred to our unit for medication adjustment after a 2-year gradual worsening of psychotic symptoms characterized by thought disturbance and behavioral disorganization. As a result of his worsening symptoms, 3 months before admission, S.P. went from living independently in a supervised care setting to requiring close supervision and help with activities of daily living. Two months before admission, he stopped bathing and washing his clothes and refused to socialize. S.P.'s relationship with his case manager, which had previously been good, ...

show abstract

Section: Discussionmentioning

confidence: 99%

Rechallenging With Clozapine Following Neutropenia: Treatment Options for Refractory Schizophrenia

Ghaznavi¹,

Nakic²,

Rao³

et al. 2008

AJP

View full text Add to dashboard Cite

show abstract

“…A 1998 report noted that up to 11% of inpatients with schizophrenia were receiveing adjunct lithium. Although its use decreased in the late 1990s, it is still commonly prescribed, particularly as an adjunct to clozapine (15). Recently a large meta-analysis of 20 randomized controlled trials examining lithium (as a sole or an adjunctive compound) in participants with schizophrenia was published.…”

Section: Introductionmentioning

confidence: 99%

“…Only a few retrospective reports exist for combination treatments with these agents to clozapine and few have included a control group (15,17,18). This study examines the efficacy and safety of the use of adjunct divalproex or lithium with clozapine vs. clozapine alone in people with treatment-resistant schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Adjunct Divalproex or Lithium to Clozapine in Treatment-Resistant Schizophrenia

et al. 2006

View full text Add to dashboard Cite

This retrospective study examined adjunct divalproex (N = 15) or lithium (N = 9) in treatment-resistant schizophrenia patients added to clozapine and compared to clozapine monotherapy (N = 25). Six month total BPRS scores were similarly improved in all treatment groups, however significantly greater improvements occurred in the first month for those on divalproex (-9) or lithium (-8) vs. clozapine alone (-4.5) (F = 3.32, df = 10.43, p = 0.0003). Rates of sedation, tachycardia, orthostasis, GI disturbances, confusion and dizziness were similar among groups. Mean weight gain was 8.7 pounds for clozapine monotherapy, 3.0 pounds in the adjunct divalproex group and 13.3 pounds in the adjunct lithium group (P = NS). A trend was noted for greater increases in blood glucose levels for those treated with adjunct lithium (F = 2.62, df = 2.28, p = 0.09). The addition of divalproex was significantly more effective in reducing global symptoms (driven by hostility and anxiety) in the first month of adjunct treatment as compared to clozapine monotherapy and to previous clozapine treatment.

show abstract

“…1 A recent retrospective study suggests that combination therapy with lithium and clozapine may provide improved treatment of psychosis in some individuals. 20 In addition, this study provides anecdotal evidence that long-term combination treatment is well tolerated. There are multiple case reports detailing the use of lithium in chemotherapy-induced leukopenia before the availability of G-CSF, the most recent published in 2001.…”

Section: Discussionmentioning

confidence: 81%

“…18,19 In contrast, lithium is inexpensive, available in oral formulations, and potentially efficacious for common comorbid illnesses in patients with schizophrenia. 20 Lithium-induced leukocytosis was reported shortly after lithium was approved in 1970 for the treatment of bipolar affective disorder. 1 The exact mechanism of lithium-induced leukocytosis is unknown.…”

Section: Discussionmentioning

confidence: 99%