Oleg V. Tcheremissine, MD, and Danielle Englert, MD
Dr. Tcheremissine is Research Director, Department of Psychiatry and Behavioral Sciences, Carolinas Healthcare System; Dr. Englert is Director of Deep Brain Stimulation Program Center for Parkinson’s Disease and Movement Disorders, Department of Neurology
Carolinas Healthcare System, Charlotte, North Carolina.

Innov Clin Neurosci. 2013;10(9–10):10–14

Funding/financial disclosures: No funding was received for the preparation of this article. Dr. Tcheremissine currently or in the past three years has received funding from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, EnVivo, Lundbeck, Otsuka, and Targacept. He curreently or in the past three years has received honoraria from Otsuka.

Dear Editor:

Schizophrenia is a chronic neuropsychiatric disorder that affects approximately one percent of the population worldwide.[1] Since the introduction of the first-generation of antipsychotics in the 1950s, the pharmacological approach has become the most widely accepted therapeutic modality for the treatment of schizophrenia.[2] The advances in neurosciences and drug development broadened the armamentarium available to clinicians. Today, there are 20 antipsychotic medications approved by the United States Food and Drug Administration (FDA) for the treatment of schizophrenia. Lurasidone is a novel psychotropic agent with D2 receptor and 5-HT2A antagonistic properties. It also has a very high affinity to 5-HT7 receptor and moderate partial agonist effects at the 5-HT1A and moderately potent antagonist effects at alpha2C receptor.[3]

Case report. A 41-year-old Caucasian man with history of schizophrenia, paranoid type, and neuroleptic-induced parkinsonism presented for the initial psychiatric evaluation per recommendations of his neurologist accompanied by his mother. During the past 20 years, the patient had nine admissions to psychiatric hospitals and was treated with a wide range of first- and second-generation antipsychotics. For the first 10 years, haloperidol was the most effective. Trials of ziprasidone and aripiprazole resulted in severe parkinsonism; clozapine and quetiapine caused severe cases of priapism, which required surgical intervention. Without antipsychotic medications, he had increasing hallucinations and paranoia, with only minimal improvement in his mobility. Anticholinergics were minimally effective and caused dry mouth and cognitive impairment.

During the initial psychiatric examination, the patient presented on a combination of olanzapine 5mg and zolpidem 10mg (at bedtime), risperidone 0.5mg, cyclobenzaprine 10mg, benztropine 1mg (twice daily), lorazepam 1mg (three times daily), and amphetamine and dextroamphetamine 10mg (once daily). He appeared at his biological age, pleasant, and cooperative. His face was moderately masked; an intermittent tremor in his chin and resting tremor in his arms and legs bilaterally was noted. He had difficulties ambulating due to stiffness and muscle rigidity, his posture was stooped, and his gait was unsteady and wide; he required assistance to get in and out of the chair. Due to severe dysarthria and drooling, his speech was decreased in rate, tone, and volume. His language skills remained adequate. His mood was euthymic and affect was flat. His thought process was logical, organized, and goal-directed; his thought content was negative for suicidal and homicidal ideations, delusional beliefs, and paranoid ideations. He reported auditory hallucinations, but no visual and tactile hallucinations. He displayed no major cognitive symptoms. His overall insight and social judgment were considered as fair. In addition to transient symptoms of psychosis and parkinsonism, he reported mild irritability and tachycardia. The patient reported no difficulties falling asleep.

After weighing the risks and benefits, zolpidem, stimulants, and risperidone were discontinued, and a trial of lurasidone 40mg at bedtime was initiated. During the next 12 months, the patient and his mother independently reported that the patient was able once again to feed and dress himself. He began using his computer and walked with his care provider to a local library. He had less difficulties in articulation and pronunciation. The overall spasticity decreased and tremor in upper extremities subsided. He regained some motor strength in his lower extremities and was able to ambulate faster. His gait improved as well.

Discussion. The wide range of adverse effects and extensive similarities in side-effect profiles between first- and second-generation antipsychotics continues to present practitioners, patients, and their families with formable challenges. In many instances, combining psychotropic medications is a common therapeutic approach.[4] Therefore, in our view, despite the polypharmacy discussed above, the presented case further highlights the unmet therapeutic needs in developing a new generation of antipsychotics with improved safety profile across the range.[5]

1. Mura G, Petretto DR, Bhat KM, Carta MG. Schizophrenia: from epidemiology to rehabilitation. Clin Pract Epidemiol Ment Health. 2012;8:52–66.
2. Carpenter WT, Davis JM. Another view of the history of antipsychotic drug discovery and development. Mol Psychiatry. 2012;17(12):1168–1173.
3. Nasrallah HA, Silva R, Phillips D, et al. Lurasidone for the treatment of acutely psychotic patients with schizophrenia: a 6-week, randomized, placebo-controlled study. J Psychiatry Res. 2013;47(5):670–677.
4. Ballon J, Stroup TS. Polypharmacy for schizophrenia. Curr Opin Psychiatry. 2013;26(2):208–2103.
5. Miyake N, Miyamoto S, Jarskog LF. New serotonin/dopamine antagonists for the treatment of schizophrenia: Are we making real progress? Clin Schizophr Relat Psychoses. 2012;6(3):122–133