Lurasidone-induced anemia: Is there a need for hematological monitoring?

Lurasidone is a newer drug used for treating schizophrenia and depression in bipolar disorder. Although comparatively safe, some side effects can occur with its use such as akathisia, extrapyramidal reaction, metabolic syndrome, and hyperprolactinemia. Blood dyscrasia with lurasidone is rarely reported in the literature except for few case reports. We present two cases of schizophrenia, treated with lurasidone developing anemia after variable period of treatment and reverting after stopping lurasidone. These cases emphasize the timely monitoring of blood parameters for prevention or early detection of anemia in patients treated with lurasidone. Copyright:

Introduction

Lurasidone is a benzisothiazol-derivative, second-generation antipsychotic and is similar in the mechanism of action to the other atypical antipsychotics. In October 2010, lurasidone was first approved for treating schizophrenia in adults. It antagonizes not only dopamine D2 receptors but also serotonin 5-HT2A and 5-HT7 receptors.[1] It has partial agonistic action at 5-HT1A receptor also. Lurasidone is comparatively a new drug approved by the Food and Drug Administration for use in bipolar depression. Usual recommended dose in the beginning is 40 mg once a day, and good efficacy is found in schizophrenia across a dose range of 40–160 mg/day. It is indicated as monotherapy for adults having bipolar depression (depressive episode of bipolar I disorder) in the dose of 20 mg per day initially which can be increased if needed, not exceeding 120 mg/day. It can also be used as an adjuvant in bipolar depression. It is considered to be a relatively safe drug having very few adverse effects. Extrapyramidal reaction, akathisia, and sedation are the common side effects with its use.[2] Although anemia is a known adverse effect, its prevalence is not studied till date. Literature shows very few case reports mentioning anemia as an adverse reaction caused by lurasidone. On the other hand, continuous and severe psychiatric illnesses such as schizophrenia and bipolar disorder may be associated with increased prevalence of anemia and nutritional deficiencies secondary to poor eating habits. It may therefore become necessary to assess blood counts of patients who receive lurasidone at baseline and on follow-up.

Cases

We present two patients diagnosed with schizophrenia developing anemia after treatment with lurasidone. First one was a 29-year-old male patient with an International Classification of Diseases 10 diagnosis of schizophrenia, paranoid type. It was a first episode with no history of psychiatric illness in the past. The patient was started on lurasidone 40 mg as monotherapy along with low dose (2 mg) lorazepam for inducing sleep. Patient's baseline investigations were within normal limit with hemoglobin (Hb) of 13.4 gm% with normal mean corpuscular volume (MCV). The patient showed improvement in symptoms within a month of beginning the treatment. However, after around 2 months of therapy, he started having weakness, lethargy, dyspnea on exertion, and giddiness. On examination, pallor was evident, so repeat blood count was advised. Hb was 6.5 gm% with raised MCV level. Test of sickling was negative, and other parameters/blood counts were within normal limits. Other blood investigations also revealed no abnormality. The patient did not have history of blood loss or other causes, leading to anemia. Considering no other causes except possibility of drug-induced anemia, lurasidone was stopped (the patient was not taking any other medications) and olanzapine was given along with supportive management for anemia from a physician (iron supplementation was given for initial 1 month). Within a month, Hb increased to 9.1 gm%, which increased to 12 gm% after around 2.5 months and no blood transfusion was required. The patient was then maintained on olanzapine 15 mg/day. Second was a 50-year-old male patient with a diagnosis of schizophrenia for around 20 years. This patient had resistant schizophrenia and was given clozapine, but he could not tolerate the drug (because of excessive sedation and salivation with a dose of 100 mg); hence, he was prescribed lurasidone with an initial dose of 40 mg/day which later increased to 80 mg/day along with blonanserin 8 mg in divided doses. The patient was maintained on these medications with reduction in positive and negative syndrome scale for schizophrenia (PANSS) score to more than 70% after 6 months of treatment compared to baseline. The patient also had diabetes mellitus and hypertension and was on treatment for the same from the physician. Initial blood investigations of this patient were within normal limits with Hb of 15.5 gm% and normal value for corpuscular volume. After around 10 months of treatment, during follow-up, the patient had complaints of giddiness, generalized weakness, and easy fatigability. Pallor was evident on general examination with no finding on systemic examination. Liver and spleen were not palpable. On investigations, kidney/liver functions and other tests did not reveal any abnormality, but Hb was 6.6 gm% with minor changes in corpuscular volume. Patient's serum ferritin and iron levels were reduced (5.10 ng/ml and 14 μg/dl, respectively) with normal total iron-binding capacity. After excluding other causes, possibility of lurasidone-induced anemia was considered. Dose of lurasidone was reduced and later stopped. The patient was prescribed aripiprazole 5 mg (later increased slowly to 30 mg/day) along with continuation of blonanserin in the same dose. Patients' repeat investigations after a month showed increased Hb to 8.9 gm% which later increased to 12.2 gm% after 3 months. Corpuscular volume also came to normal level. This patient though did not show improvement as before (with lurasidone), PANSS score reduced to 50% compared to the initial reading. Iron supplementation was given for initial one month which was stopped later on, and the patient was advised regular follow-up. With Naranjo algorithm (adverse drug reaction probability scale), the score was 5 in both the cases. That is in “probable” range.

Discussion

Currently available literature indicates that lurasidone is well tolerated (having less adverse effects) and effective medication for the treatment of schizophrenia and bipolar depression in the short term. It is associated with reduced risk for weight gain, cardiac abnormalities, and metabolic side effects, but the risk of causing akathisia can be much more than many other atypical antipsychotic agents.[3] There are various studies in the literature mentioning adverse effects due to lurasidone though the propensity is low. These side effects include extrapyramidal reaction, metabolic syndrome, hyperprolactinemia, and akathisia.

In patients described above, besides anemia, no other side effects were observed. In literature, blood dyscrasia is mentioned as adverse reactions due to lurasidone. Authors have reported thrombocytopenia in a patient with bipolar depression who had received 80 mg/day of lurasidone for 2.5 months.[4] Few case reports also mentioned agranulocytosis as a dose-dependent adverse effect of lurasidone, which reverted after reducing the dose.[5] Anemia is rarely reported as an adverse effect; one study has observed the occurrence of anemia with the use of lurasidone during premarketing evaluation of the drug.[6] As per the “medicine updates,” frequency of anemia caused by lurasidone is not known.[7] Our patients developed anemia after 2 months and 10 months of lurasidone treatment, respectively, which suggests that anemia can occur after variable period of therapy. Antipsychotic agents are known to cause changes in the metabolism of iron and increase its uptake in the brain, leading to iron deficiency anemia. The literature is not available that describes the duration of lurasidone therapy after which the anemia can occur. The mechanism by which the anemia occurs (secondary to lurasidone) is also not clear, but drug-induced myelosuppression can be one of the possibilities though other blood parameters were in normal range. There was a significant reduction in Hb level in both the patients; this in turn increases the importance of timely testing of blood parameters. Furthermore, both the patients improved in variable period after stopping the drug. This indicates the reversibility of this side effect. Rechallenge with lurasidone was not done as both the patients as well as their relatives were not willing for the same. In addition, literature mentions that blood disorders caused by drugs are potentially dangerous and it is not recommended to rechallenge with a causative or suspected agent just to confirm the causality.[8]

At present, there are no guidelines for monitoring blood parameters in patients treated with lurasidone, but some manufacturer recommends performing complete hematological count and differential count in patients whose existing white blood cell count is already low or they have a history of drug-induced neutropenia or leukopenia. Case reports in our article clearly suggest the importance and need for estimating blood parameters at baseline and on follow-up, though the frequency of testing can be variable.

Conclusion

Lurasidone, though comparatively a safer drug with respect to the adverse reactions, monitoring for the side effects should always be done. It is a newer antipsychotic drug, and anemia secondary to its use is rarely reported. Monitoring of blood parameters can help in the prevention or early detection of anemia so that timely intervention can be done. It was not possible to interpret when and how frequently the monitoring should be done.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.