Adverse Drug Event

Journal of Pharmacy Practice

1-4
Hallucinogen Persisting Perception The Author(s) 2015
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Disorder and Risk of Suicide DOI: 10.1177/0897190014566314
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Joy Brodrick, PharmD1, and Brian G. Mitchell, PharmD, BCPS, BCPP1,2

Abstract
A 30-year-old male patient developed a hallucinogen persisting perception disorder (HPPD) after smoking cannabis laced with
phencyclidine (PCP) or lysergic acid diethylamide (LSD) 10 years prior to hospital admission. Clinically, he reported seeing vivid,
saturated colors and caricature-like objects. The patient described perceiving objects or people in motion as moving faster than
normal. He reported living in a dream-like state and feeling numb and detached from other people and his surroundings. Upon
pharmacotherapy initiation, facility transfer, and subsequent discharge from an acute psychiatry unit, he ultimately committed
suicide. Although hallucinogen abuse is common in the United States, this case suggests that HPPD maybe significantly underdiag-
nosed and undertreated. In some cases, this oversight may perpetuate years of unnecessary patient suffering and can ultimately
lead to severe depression and suicide.

Keywords
hallucinogen persistent perception disorder, hallucinogen, mortality, death, suicide

Introduction
The primary characteristic of hallucinogen persisting percep-
tion disorder (HPPD) is the recurrence of the perception dis-
turbances that were experienced while the individual was
intoxicated with the hallucinogen.1 The clinical relevance
of long-term psychological flashbacks remains unclear as
earlier studies mention flashback incidence rates of 5% to
54%, while more recent reports suggest that this range may
be exaggerated.2-4 Epidemiological information about HPPD
is lacking; however, people suffering from HPPD appear to
be predominantly male and develop HPPD symptoms during
their adolescent years.5,6 Previous literature suggest that the
prevalence of HPPD is probably low but may be difficult to
estimate given limited hallucinogenic drug use in the general
population, and reluctance to seek treatment because of fear
of prosecution, guilt, and/or stigmatization.7 Baggott et al
found that 4.2% of patients described their visual experiences
as initially or currently troublesome enough to have prompted
thoughts of treatment but only 1.1% of patients actually
sought treatment.8 High comorbidity with other conditions
such as anxiety, panic, decreased attention, and depersonali-
zation/derealization (DP/DR) in newer reported cases of
HPPD suggest a relationship of these conditions with visual
perception.9 The implications of other psychiatric conditions
illustrate that HPPD is not limited to the visual system and
that multiple brain areas may be involved.9 Outcomes data
from treatment of HPPD and mortality rates secondary to
HPPD are lacking. Suicide attempts and completion rates as
a result of acute or chronic HPPD have also not been
explored.
Method
A literature search using Pubmed, Medline, and EBSCO was
conducted on July 4, 2014, using the search terms hallucinogen
persistent perception disorder, hallucinogen, mortality, death,
and suicide.
Case Report
A 30-year-old male, native to Bosnia, presented to the emer-
gency department after surviving two subsequent suicide
attempts by hanging. The patient was visiting the area when
he twice attempted to hang himself with a necktie in his
brothers home. Just before losing consciousness, he became
frightened and decided to drive himself to the hospital for help.
A psychiatric history of depression and bipolar disorder was
reported. The patient also reported history of trauma in which,
as a child, he witnessed friends and relatives brutally murdered
in the Kosovo War.
The patients family history was insignificant for chronic
diseases such as diabetes, hypertension, hyperlipidemia,
1
Department of Pharmacy, Michael E. DeBakey Veterans Affairs Medical
Center, Houston, TX, USA
2
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College
of Medicine, Houston, TX, USA
Corresponding Author:
Brian G. Mitchell, Menninger Department of Psychiatry and Behavioral
Sciences, Baylor College of Medicine, One Baylor Plaza, MS, BCM 350,
Houston, TX 77030, USA.
Email: brian.mitchell3@va.gov

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2 Journal of Pharmacy Practice
myocardial infarction, stroke, cancer, and substance abuse. His
father was also uncertain about whether mental illness such as
bipolar disorder occurred in the family history, as most of the
family was killed during the Bosnian War. The patient denied
recent alcohol or drug use but endorsed a remote illicit sub-
stance use 10 years prior when he smoked cannabis that was
presumably laced with lysergic acid diethylamide (LSD) or
phencyclidine (PCP). The patients father also reported that the
patient had previously used cocaine during the 1990s as well
but was unsure of the duration. Since the time the patient
smoked cannabis, he had visual perception distortions or
flashbacks similar to the acute effects experienced after
ingesting the hallucinogen.
He reported seeing vivid, saturated colors and caricature-
like objects (macro-/micropsia). He described seeing every
little detail of something and perceiving objects or people
in motion as moving faster than normal (akinetopsia). He
reported living in a dream-like state (derealization) and feel-
ing numb and detached (dissociation) from other people and his
surroundings. His perceptual distortions were continuous, but
he was often able to distract himself by concentrating on
schoolwork. Since finishing his masters degree he had become
progressively more depressed and isolative. He reported feel-
ing sad and having decreased energy, loss of appetite, and per-
sistent suicidal ideation.
The patient reported having no known drug allergies. His
past medication history included minimal response to a variety
of psychotropic medications. The patient had a history of neg-
ative responses to antipsychotic treatments. In the month prior
to this admission, the patient had been discharged from another
inpatient psychiatric facility (after admission for a third suicide
attempt) with an Axis I diagnosis of bipolar disorder. During
that admission, brain magnetic resonance imaging revealed
nonspecific findings of scattered foci of T2/fluid-attenuated
inversion recovery (FLAIR) signal abnormality.
Upon this hospital admission, a urinary drug screen was
unable to be obtained and vital signs were within normal limits.
The mental state examination was significant for psychomotor
retardation, restricted affect, and depressed mood. The patient
exhibited goal-directed and logical thought process, except
when speaking about his perceptual disturbances. His global
assessment of functioning (GAF) score was 30, indicating seri-
ous impairment.
Titration of selective serotonin reuptake inhibitor (SSRI),
citalopram, was attempted for treatment of recurrent, severe
major depressive disorder. The patient received citalopram 40
mg daily and was continued on his other home medications,
lamotrigine 50 mg daily and mirtazapine 15 mg at bedtime. Over
the next 2 days, he reported no improvement in visual distur-
bances, depressive symptoms, or suicidal thoughts. The patient
was pleasant although minimally interactive, hypersomnolent,
and isolative to his room. Following a literature review, the
clinical pharmacist suggested HPPD as a possible diagnosis
and presented limited evidence on levetiracetam for treatment.
However, on his third day of inpatient stay, the patient was found
to be ineligible for services within the health care system and
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was transferred to a nearby county hospital for psychiatric care.
The patient was transferred with an Axis I diagnosis of Severe
and Recurrent Major Depressive Disorder, Bipolar Disorder by
history, Perception Disorder (unclear etiology).
Subsequently following hospital transfer, the patient failed
to keep his outpatient mental health clinic appointments and
could not be contacted by hospital staff members. In the fol-
lowing month, a hospital staff employee attempted to call the
patients cell phone, which instead was answered by his father.
The father reported that the patient had completed suicide one
week following transfer to the county psychiatric facility.
Discussion
The hallmark sign of HPPD is reexperiencing, when a person is
sober, of the perceptual disturbances experienced while the
person was intoxicated with a hallucinogen. Visual distortions,
including false perceptions of movement, intensified colors,
and macropsia or micropsia, tend to be predominant.1 This
patient exhibited several of these symptoms as well as clini-
cally significant distress and impairment in functioning. No
other medical or mental disorders were identified to explain the
patients persistent symptoms.
Continuous visual distortions associated with HPPD can
lead a person to feel a loss of reality and detachment from the
surrounding world, ultimately contributing to anxiety, depres-
sion, and suicidal thoughts. Our patient exhibited signs of dis-
sociation and detachment. The severity of his depression and
despair ultimately led to suicide completion. Unfortunately,
there is weak evidence for successful management of HPPD.
No cure or definitive effective treatment exists. For this reason,
psychotherapy can be very important in enabling patients to
cope with their symptoms and lead normal lives.
Our patient reported good historical response to Selective
Serotonin Reuptake Inhibitors (SSRIs). One case report suggests
near remittal of visual disturbances with sertraline 100 mg daily
treatment in a 22-year-old male with HPPD and mild depres-
sion.10 Our patient also reported worsening visual problems with
risperidone treatment. Three case reports demonstrated intensi-
fication of anxiety and visual disturbances after risperidone use
in patients with HPPD.11 The adverse effect of risperidone may
be related to its blocking effects at the 5-hydroxytryptamine 2
(5-HT2) receptor, resulting in decreased gamma-aminobutyric
acid (GABA) activity and intensification of visual symptoms.
Our patient was on a low dose of lamotrigine 50 mg daily upon
admission to the hospital. There is weak evidence for lamotri-
gine use from a case report of a young female having HPPD,
depression, and suicidal ideation. After 6 months on lamotrigine
200 mg daily, followed by 6 months on lamotrigine 100 mg
daily, the patient reported total resolution of macropsia and
micropsia and significant improvement in motion and light
perception.12 Clonazepam, clonidine, and levetiracetam
have the strongest evidence for pharmacological treatment
of HPPD.13-15 Each of these agents has demonstrated reduc-
tion in or complete resolution of symptoms in at least one
prospective study of patients with HPPD.
Brodrick and Mitchell
Another factor that needs to be addressed in this case is the
length of hospital stay related to the completion of the patients
suicide. Data over time have shown that mental illness, sub-
stance abuse, and addiction are associated with an increased
risk of suicide and that 90% of people who commit suicide
have been diagnosed with a mental illness.16 Suicide risk and
suicide attempt are indicators of a need for hospitalization.
Hospitalization can mitigate this risk, but since the majority
of psychiatric disorders are chronic, patients can relapse from
their suicidal ideations and kill themselves when not in hospi-
tal.17 Our patient had a history of previous suicide attempts and
a suicide attempt prompted his admission to our facility.
Despite the fact that our patient wasnt eligible for services
within our health care system, he was able to be transferred
to another psychiatric treatment facility without any interrup-
tion in his care. However, the patients length of stay was not
long and he was discharged within a week of being admitted
to our health care system. Brief psychiatric hospitalizations
have been linked to negative outcomes in regard to patient
care.17 An ideal psychiatric admission must generally try to
reach an elusive balance. The admission should not last too
long, for it can stigmatize the admitted patient by taking that
person out of society for an extended period. However, the
admission cannot also be too brief otherwise the medical goals
of the admission cannot be fulfilled and risk of relapse (eg,
relapse of suicidal ideation or aggressive behavior) increases.17
Goldacre et al18 were concerned with cases of suicide soon
after discharge and studied this occurrence during the first year
after discharge from a psychiatric inpatient care. Reviewing a
database of the Oxford Regional Health Authority area, they
found 14 240 individuals aged 15 years and older had a total
of 26 864 admissions to psychiatric hospitals. From those
admissions, 134 (0.9%) died by suicide in the year following
discharge. They concluded that the month after discharge pro-
poses the highest risk and that specifically for men, the first day
is the most crucial, with twice as high a risk of suicide com-
pared to the rest of the month.18 Several dynamics could be
generated by from these data such as patients having a per-
ceived loss of support, reduced supervision, relapse because
of renewed exposure to problems in the home environment,
withdrawal of drug therapy, or the fact that the patient is still
unwell. Literature supports multicomponent interventions to
produce safer community transition following inpatient psy-
chiatric admission.19-23 Interventions include psycho- and
medication education, postdischarge telephone follow-up,
assertive community treatment, and other forms of intensive
care management.
Conclusion
Literature reports suggests that HPPD may affect more than
50% of hallucinogen users.8 It can be a chronic and debilitating
condition; however, many individuals are able to suppress the
visual disturbances and continue to function normally. HPPD
has been included in the Diagnostic and Statistical Manual
of Mental Disorders since 1980s; however, our patients
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3
treatment team was unfamiliar with the condition and unaware
of the mortality risk associated with the condition. Although
hallucinogen abuse is common in the United States, this case
suggests that HPPD may be significantly underdiagnosed. In
some cases, this oversight may perpetuate years of unnecessary
patient suffering. In the worst case, untreated HPPD can lead to
severe depression and mortality.
Acknowledgments
The authors would like to thank Lisa Miller, PharmD, BCPP, CGP, for
serving as the primary clinical pharmacy preceptor during the
patients admission to our health care facility.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship,
and/or publication of this article.
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