Supplementary Table: Clinical details of oculogyric crisis cases
Case 1
A 22-year-old Caucasian woman with a diagnosis of schizoaffective disorder and a history of
bulimia and depression had a complicated course of antipsychotic switches, illness
recurrences, and OGC episodes. Her prototypical OGC episode was 20-60 minutes in duration
that recurred at a frequency of 1-5 times per month. Follow-up details were available for a
total of 7 years, 2 years in the NSEPP clinic and 5 years with a community mental health team
and direct contact with the patient. Her first OGC experience occurred 4 days after hospital
admission in which she received loxapine 50 mg/day for 3 days and single doses of olanzapine
and quetiapine. Thirteen days prior to admission she had been given her regular
intramuscular dose of long acting risperidone 25 mg, which she had been treated
continuously with for 13 months. In the following 2 years, recurrences of OGC were frequent,
resulting in a pattern of antipsychotic (risperidone, olanzapine, and quetiapine) and mood
stabilizer (lithium, valproate, lamotrigine) switches, dosage reductions, symptom relapses,
and hospitalizations. OGC episodes were more often experienced when taking more than one
antipsychotic, during illness exacerbations or therapy switches. Use of oral benztropine 2 mg
attenuated the episodes. Paradoxically, following one hospital admission she experienced
several OGC episodes that onset after olanzapine had been reduced to 5 mg/day and
recurred for 4 weeks after its discontinuation, each lasting approximately 45 minutes. After 2
years with the community team, with OGC episodes continuing while treated with quetiapine
and valproic acid, she experienced several OGC episodes during an overlapping switch to
aripiprazole. She lived with recurrent OGC episodes, monthly or more often, throughout 5
years of antipsychotic treatment. The episodes stopped gradually over time after stopping
aripiprazole and starting the Niaspan® formulation of niacin. She has been without any
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episodes for 2 years but describes periodic episodes of eye muscle strain and fear of
recurrences.
Case 2
A 22-year-old South Asian man with a diagnosis of schizophrenia and a history head injury
was treated with olanzapine 17.5 mg/day for 10 months before experiencing his first episode
of OGC lasting 20 minutes. Gradual dose reduction was associated with a reduction in
symptom severity but episodes persisted at a rate of 1-2/week each persisting for 5-10
minutes. Prodromal symptoms included pain and tension in his forehead and “flicking up” of
his eyes two minutes before the full onset of the episode. Over the following year he
remained on olanzapine with one dose fluctuation due to symptom exacerbations. A trial of
quetiapine failed due to inefficacy. When olanzapine treatment resumed OGC worsened,
occurring twice weekly, usually in the evening, for up to 4 hours in duration with brief
intermittent periods of relief. He described the episodes as particularly distressing for exam
writing and evening activities. Unsuccessful remedial efforts included a switch in olanzapine
formulation, timing, and daily dose; daily benztropine (≤3 mg/day), daily vitamin E 400
IU/day, diphenhydramine 50 mg/episode, and lorazepam ≤1 mg/episode. Eighteen months
after the initial OGC, he was switched to clozapine. During the cross-titration there was a
period of worsening OGC, in which he experienced up to 3 episodes per day over a 2 week
period. After 4 years of treatment with clozapine, he continued to experience mild OGC
episodes at a rate of once per week.
Case 3
A 24-year-old Caucasian man with a diagnosis of schizophrenia first experienced OGC after 2
years treatment with olanzapine 20 mg/day. He experienced 2-3 episodes of OGC per week of
up to 30 minutes in duration over 2 months. The dose of olanzapine was then reduced
resulting in a reduction in episode frequency, duration, and intensity. Episodes resolved for
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one month when switched to 10 mg/day of olanzapine oral dissolving tablets. When OGC
episodes recurred the dose was further reduced to 7.5 mg/day, which was associated with
another temporary interruption of episodes and an exacerbation of psychotic symptoms. At a
dose of 10 mg/day he experienced another OGC episode. Two months later, he was switched
to quetiapine and eventually stabilized on 600 mg/day and valproic acid 1000 mg/day. Over
the following 5 years he experienced no further OGC episodes.
Case 4
A 19-year-old African Canadian man with a diagnosis of schizophrenia experienced his initial
OGC episode after 5 months of treatment with olanzapine 20 mg/day and fluoxetine 20
mg/day. Prior to this combination he received a short course of risperidone that was stopped
due to adverse effects. He described a fixed upward stare, rapid blinking, and no ability to
voluntarily control his eye movement. He denied pain or other movement disorders.
Recurrences eventually became daily lasting 10 minutes to 4 hours. He indicated he could feel
episodes “coming on”. The prodrome involved a fixed stare lasting 15 to 60 minutes with the
urge to have his eyes deviate upward and a feeling of pressure behind the eyes. He described
the episodes as very distressing, interfering with school, and typically occurred in the
afternoon or early evening. A dose reduction of olanzapine was associated with a relapse in
psychotic symptoms that prompted a trial of ziprasidone 160 mg/day. Later, quetiapine was
added to ziprasidone to augment treatment response. OGC episodes persisted at a rate of
twice weekly and were aborted with variable success with benztropine 1 mg,
diphenhydramine 50 mg, or lorazepam 0.5-1 mg. He experienced OGC episode recurrences
for 2 years. When admitted due to a relapse of manic symptoms he was switched to
clozapine to which he responded well and experienced no further OGC episodes over the
following 3 years.
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Case 5
A 24-year-old Caucasian woman with a diagnosis of schizoaffective disorder experienced 6
distinct tardive-onset OGC episodes that occurred over a 2 month period each lasting 1 to 2
hours. Prior to her first episode, she had been treated with biweekly injections of long-acting
intramuscular risperidone for one year and quetiapine 200 mg/day for two weeks. With the
first OGC episode, she described experiencing a sudden-onset, fixed upward gaze with
associated nausea and no other movement disorders. The second episode occurred the next
evening after receiving a biweekly dose of risperidone. Quetiapine was discontinued and oral
risperidone 0.5 mg/day was added shortly thereafter and later discontinued. One month
later, she experienced two episodes of OGC, one while driving with her young child, within
hours of a risperidone injection. Symptoms resolved 30 minutes after taking benztropine. Five
days later, after adding benztropine 1 mg twice daily and 2 mg as needed, she experienced an
OGC episode that persisted for 60 minutes with brief, intermittent periods of symptom relief.
Risperidone was stopped following a second episode of OGC while driving. Concerned about
being unmedicated, she started risperidone 1.5 mg/day and subsequently experienced
another OGC 11 days later while driving with her young child in the car. This episode
persisted for 2 hours and caused her a great amount of distress. Risperidone was stopped and
benztropine 1 mg twice daily was continued for several days. Prodromal symptoms per
episode included blurry vision and seeing spots. She experienced no further OGC episodes in
the following 2 years. During this time she avoided antipsychotic medication, with the
exception of a brief trial of aripiprazole that was not tolerated.
Case 6
A 15-year-old Caucasian boy with a diagnosis of schizophrenia (likely childhood onset) and
mild-moderate intellectual disability experienced a first OGC episode within one week of
adding ziprasidone 40 mg/day to risperidone 3 mg/day treatment as a gradual cross-over
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strategy. Risperidone had been prescribed for one year with positive effect but resulted in
gynecomastia and weight gain. The initial experience happened while several city blocks from
home forcing him to bend forward to navigate his way home. He stated “my eyes were rolling
back in my head.” Ziprasidone was stopped and risperidone 3 mg/day continued and was
then switched to olanzapine 10 mg/day. During monotherapy with risperidone and
olanzapine over the following one year he experienced OGC episodes ranging from 2-3 times
per week to once monthly, each lasting up to 1 hour. Each episode required him to flex at the
neck and bend forward in order to see, with blurred vision. Parents noted his eyes appeared
to be "rolling back". Oral benztropine 1 mg helped to abbreviate the episodes, which
eventually stopped after one year. Duration of follow up was 6 years during which further
changes in medication occurred. No further experiences of OGC were reported when
switching among aripiprazole, olanzapine, quetiapine, lurasidone, and clozapine in
combination with other medications including divalproex, fluoxetine, sertraline, trazodone
and lisinopril. He was continued on clozapine with good response and no further episodes of
OCG.
Case 7
A 17-year-old African Canadian girl with a diagnosis of schizophrenia and mild intellectual
disability and a history of non-adherence to oral antipsychotics was treated with
intramuscular risperidone 37.5 mg biweekly for 7 months before experiencing a first episode
of OGC. Episodes then recurred weekly and later every two weeks ranging in duration from
10 to 40 minutes. She experienced blurred vision as a prodromal symptom of OGC. A
successful strategy that she used for interrupting an episode was to fall asleep. Oral
benztropine was also helpful. She experienced blurry vision before the upward rolling of her
eyes and stated that the events were very distressing. Over two years of follow-up,
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intramuscular risperidone was continued and she continued to experience OGC episodes
approximately every two weeks.
Case 8
A 16-year-old Caucasian girl with a diagnosis of DiGeorge syndrome (22Q11 deletion
syndrome), mild-moderate intellectual disability, and complications of the genetic syndrome
including cardiac, neurological and psychiatric, presented with psychotic symptoms and
anxiety. Due to the presence of psychosis and the high associated risk for schizophrenia with
DiGeorge syndrome (25%), she was initiated on aripiprazole for 3 months up to a dose of 25
mg/day and then switched to risperidone 2 mg/day due to suboptimal treatment response.
She experienced a first OGC episode one week after initiating the switch while on both
risperidone 1mg/day and aripiprazole 10mg/day. This recurred two more times over two
weeks during the medication crossover. Each episode involved a fixed upward stare lasting
approximately 10 minutes. She described being unable to pull her gaze downwards,
discomfort and an inability to focus. Her mother witnessed each episode, which settled
without intervention. After aripiprazole was discontinued she experienced no further
episodes. She was treated with risperidone 2 mg/day for a total of 6 months and then
quetiapine 400 mg/day for 4 months. Thereafter, antipsychotics were discontinued. Total
follow up time was 2 years.
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