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Copyrightⓒ 2010, Korean College of Neuropsychopharmacology
Case Report
Clinical Psychopharmacology and Neuroscience 2010;8(3):170-174
Appetite Suppressor Induced Psychosis
Soon-Jai Kwon2, Jong-Chul Yang1,2, Tae-Won Park1,2, Young-Chul Chung1,2
1
Department of Psychiatry, Chonbuk National University Medical School and Institute for Medical Sciences, 2Department of Psychiatry,
Chonbuk National University Hospital and Research Institute of Clinical Medicine, Jeonju, Korea
Amphetamine analogues are widely prescribed for the treatment of obesity; their therapeutic mechanisms are appetite suppression and sympathomimetic effects. However, due to their structural similarities to amphetamine, patients who take appetite
suppressants may experience psychotic symptoms such as hallucinations or paranoid mental states. We report on a patient
who had been taking the appetite suppressant, phentermine for 2 years and experienced a sudden onset of psychotic symptoms.
She had no past history of psychiatric treatment and no familial history of psychiatric illness. She experienced continuous auditory
hallucinations and paranoid delusions, without disordered thinking, and significant negative symptoms. She stopped taking medication immediately following the onset of symptoms, which lasted for about 10 days thereafter. This case illustrates that phentermine, the most commonly prescribed appetite suppressant, can cause psychotic symptoms; warnings about these possible side
effects should be made explicit to all those considering the use of appetite suppressants.
KEY WORDS: Amphetamine analogue; Diet pill; Phentermine; Psychosis.
INTRODUCTION
cuits involved in appetite, the importance of pharmacotherapy is increasing as an effective adjunctive measure,
and anti-obesity drugs are being widely prescribed all
over the world, including Korea.
Anti-obesity drugs work by acting on one of two major
mechanisms, central and peripheral. The drugs with a central mechanism control appetite by affecting brain neurotransmitters such as norepinephrine and serotonin. On the
other hand, the drugs that act on peripheral pathways influence digestion or absorption of macronutrients and
sometimes modify intermediary metabolic processes, like
lipolysis or lipogenesis.2) Amphetamine analogues, represented by phentermine, phendimetrazine and diethylpropion, are centrally acting antiobesity drugs and have
been widely prescribed since they were approved by the
FDA in 1960, due to their outstanding antiobesity effect
2,3)
and minimal side effects. Table 1 summarizes the amphetamine analogues commonly prescribed in Korea.
Since the approval of amphetamine analogues by the
FDA, several cases of psychotic symptoms induced by
amphetamine analogues have been reported.4-8) In Asia,
two cases have been reported of psychotic symptoms
9,10)
brought on by amphetamine analogues.
Here we report on a 35 year-old woman who experienced
psychotic symptoms after taking phentermine for 2 years.
Obesity has become a global issue due to its potent danger to public health; it is known to have a causal effect on
metabolic syndrome as well as cardiovascular diseases.
There has been a marked increase in levels of obesity
amongst people in Korea, accompanied by rapid socioeconomic development and lifestyle modification. One
large cohort study performed in Korea indicated that the
mean BMI had increased by 0.8 kg/m2 in men and by 0.3
2
kg/m in women between 1992 and 2000. The BMI
change showed the steepest slope amongst the youngest
men (0.2 kg/m2 per year).1) Thus, the treatment of obesity
has become a contemporary social issue in Korea.
Lifestyle modifications that balance energy intake and
expenditure are thought to be fundamental to the treatment
of obesity. However, in some people, lifestyle modification is hard to achieve and it is not always thought to
be a sufficient means of treating the problem. Due to recent major advances in our knowledge of the neural cirReceived: August 20, 2010 / Revised: November 4, 2010
Accepted: December 2, 2010
Address for correspondence: Young-Chul Chung, MD, PhD
Department of Psychiatry, Research Institute of Clinical Medicine,
Chonbuk National University Hospital, Geumam-dong, Jeonju
561-712, Korea
Tel: +82-63-250-2185, Fax: +82-63-275-3157
E-mail: [email protected]
170
Appetite Suppressor Induced Psychosis 171
Table 1. Amphetamine analogues prescribed as antiobesity drug in Korea
Trade name
Panbesy SR
Phentermine Kukje
Nobse
Dietamin
Retis
Metamax
Vitupen
Sinsphen
Adipex
Weltmine
Fastin
Penmin
Phenkini
Pentmin
Primin
Lofat
Dietrin
Adpen
Phendirazine
Phendithin
Fenslim
Phentin
Phenhold
Dipion
Wellpion
Tenuate
Dosage
(mg)
Main ingredient
30
37.5
37.5
37.5
37.5
37.5
37.5
37.5
37.5
37.5
37.5
37.5
37.5
37.5
37.5
37.5
35
35
35
35
35
35
35
25
25
25
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phentermine hydrochloride
Phendimetrazine tartrate
Phendimetrazine tartrate
Phendimetrazine tartrate
Phendimetrazine tartrate
Phendimetrazine tartrate
Phendimetrazine tartrate
Phendimetrazine tartrate
Diethylpropion hydrochloride
Diethylpropion hydrochloride
Diethylpropion hydrochloride
CASE
The patient was a 35 year-old woman who had worked
in a bar in Gang-won province for the past eighteen
months. She had divorced her husband 8 years ago, following an infidelity. She had no psychiatric treatment history and no family history of psychiatric disease. She was
polite, with good manners, and usually got on well with
her family and friends. Before she married, she had
worked as an aerobics instructor. According to her family,
she was sometimes overly concerned about her body
shape, although she did not appear to be overweight. In
2007, she started taking 37.5 mg of phentermine, prescribed by her gynecologist, to control her body weight.
Her gynecologist advised her not to take the pill for a period of time after 12 consecutive weeks of medication. Up
until 2009, she had complied with the doctor’s suggestion
by having a 1-week wash-out period every 12 weeks.
However, from January 2009 she started taking the medicine continuously, without wash- out periods. Although
she had not experienced any side effects previously, other
than mild insomnia, she started to feel nervous during the
day and felt dysphoric more easily. In August 2009, she inadvertently discovered that her boss’s boyfriend was
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sleeping with another female employee. For the next couple of weeks she felt troubled about whether or not to tell
this to her boss. On August 16, just after getting out of bed
in the morning, she suddenly heard voices, although she
was alone. The voices sounded like her boss and her boss's
boyfriend whispering and they continued all day long. The
voices were usually talking to each other, commenting on
her every behavior and sometimes blaming her directly for
her unfaithfulness. She searched her room for concealed
microphones or video cameras but found none. She decided to walk out of her workplace, but the voices kept
talking to her and made her more agitated as she drove
home to Iksan. After her psychotic symptoms occurred,
she stopped taking phentermine. Even after she got home,
the voices continued and made her more anxious and
agitated. She could not sleep for more than 2∼3 hours.
She was involuntarily admitted to Chonbuk National
University hospital by her family.
When admitted, she appeared thin with a BMI of 20.3
2
kg/m . She seemed alert but quite confused and agitated.
She complained about severe anxiety and irritation but
said that her auditory hallucinations had stopped on the
day before the admission. However, she continued to display a persecutory and supervisory delusion that her boss
172
S.J. Kwon, et al.
and her boss’s boyfriend were watching her using a concealed microphone and video camera. She believed that
they were watching her because she knew too much about
their private issues. She had not taken her appetite suppressant since August 16, 5 days before admission. On admission, her scores on the Positive and Negative Synd11)
rome Scale (PANSS) and Beck Depression Inventory
Depression Inventory (BDI)12) and Mini-Mental State
Examination (MMSE)13) were 99, 17 and 30 respectively.
Results of physical examination, hematological tests including syphilis screening test, and urinalysis were
normal. In the special urinalysis test for narcotics, no positive results for amphetamine, methamine, heroin or cannabis were reported. Although she had not had any personal or familial history of possible neurological disease
or head trauma, brain MRI was recommended to rule out
neurological or organic causes. However, the patient and
her family refused a brain imaging study for economic
reasons. Although she was not showing any signs of abnormal perception, including auditory hallucination, she
had a persistent persecutory and supervisory delusion that
somebody had visited her room and tried to set up some
kind of monitoring device. Because her psychotic symptoms were related to the use of appetite suppressant, we
prescribed benzodiazepine. By the 4th day of admission,
her delusion had subsided substantially. She felt less suspicious and her feeling of being watched was reduced. She
was moved to an open ward and showed no further delusional symptoms, but watched TV in the recreational
room or chatted with other patients. However, she sometimes complained of anxiety without any particular cause.
On the 15th day of admission, the patient and her family
demanded discharge. Just before the discharge, we put her
on 5 mg/day of aripiprazole to prevent possible relapse.
Following discharge, she quickly returned to her normal
life, helping her family. Although she sometimes had transient insomnia or complained about hypersensitivity to
noise, no evidence of recurrence of psychotic symptoms,
including auditory hallucinations or delusions, was
observed. She visited the outpatient clinic twice, after
which she discontinued her visits.
DISCUSSION
Amphetamine analogues often cause sweating, dry
mouth, blurred vision, agitation and hyperactivity. Although it is rare, some cases have been reported in which appetite suppressants consisting of amphetamine analogue
have caused depressed mood, delirium and even psychotic
14)
symptoms such as hallucinations and delusions. The
possible mechanisms are related to the fact that they share
a similar molecular structure to phenethylamine, the major building block of amphetamine, and modulate release
and reuptake of dopamine. Compared to amphetamine, it
is commonly accepted that amphetamine analogues work
on norepinephrine more specifically than dopamine and,
consequently, have less potential for inducing abusive usage or psychotic symptoms. However, it must be noted
that a few studies have suggested its strong action on
dopamine. For example, it has been reported that phentermine caused a marked elevation of extracellular dopamine
15)
levels in rat nucleus accumbens. It has also been demonstrated that injections of phentermine 2 ml/kg and 5 ml/kg
increased brain dopamine concentrations by 27% and
16)
85% respectively.
Table 2 summarizes reported cases of psychotic symptoms induced by amphetamine analogue. Most of the cases were young women without any psychiatric treatment
history or family history of psychiatric illness. All of them
had taken amphetamine or amphetamine analogue for
several months. The most frequent psychotic symptoms
were auditory or visual hallucinations and delusions of
persecution or supervision, which developed abruptly.
Some cases showed mood symptoms such as depressed
mood or anhedonia and, in rare cases, disorientation.
Usually psychotic symptoms improved several days to
weeks after discontinuing amphetamine analogue usage
or after taking low doses of antipsychotics. Generally, it is
difficult to distinguish psychotic symptoms induced by
amphetamine analogue from those of schizophrenia.
However, in most cases of amphetamine-induced psychosis, patients' premorbid social functions were normal
and the psychotic symptoms subsided completely within 4
weeks of discontinuing amphetamine analogues and starting low doses of antipsychotics. This said, a few cases
have progressed to chronic psychotic disorder, although
the causal relationship with amphetamine analogues is
unclear.17) Importantly, most cases did not show associative loosening or social withdrawal symptoms, both hallmarks of schizophrenia.18) Our case also showed no associative loosening and her premorbid social functions were
well maintained. Her psychotic symptoms only lasted for
10 days and rapidly remitted a week after discontinuing
phentermine, without the use of antipsychotics. Most of
the reported cases showing psychotic symptoms had taken
more than the maximum dose of amphetamine analogue.6,7,9) In some cases, psychotic symptoms appeared after an abrupt increase in dosage of amphetamine analo-
Appetite Suppressor Induced Psychosis 173
Table 2. Summary of case reports on amphetamine analogue-induced psychosis
Author
Age/Sex
Amphetamine
analogues
Dosage/Periods
Past psychiatric
history
Symptoms
4)
33/F
Diethylpropion
Therapeutic dose
None
Carney4)
40/F
Diethylpropion
Therapeutic dose
None
Brooke et
5)
al
42/F
Diethylpropion
Therapeutic dose
1 year
None
Brooke et
al 5)
Devan6)
35/F
Diethylpropion
30 mg×25 cap
Bulimia nervosa
22/F
Phentermine
30 mg for 9 months
90 mg for 3
months
None
Cleare7)
32/F
Phentermine
30∼60 mg for 4
months
None
Auditory hallucination,
delusion of control
Zimmer et
al 8)
42/F
Phentermine/
Fenfluramine
Bipolar disorder
Depression, anhedonia,
fatigue, insomnia
31/F
Phendimetrazine
Phentermine 30 mg
Fenfluramine
60 mg for 4 days
240 mg for 2 years
720 mg for 1 year
None
Auditory hallucination,
delusion of reference,
depression
Carney
Kim et al
9)
gue.7,9) Our case had also been taking phentermine 37.5
mg/day continuously for over 7 months. Several features
of our case, described above, lead us to conclude that her
diagnosis was psychotic disorder due to abuse of amphetamine analogue.
There are several points of contention to be noted. Even
though the urine test for narcotics was normal, it was not
a specific test for phentermine. Moreover, the timing of
the test was too late, given that the half-life of phentermine
is 16 to 31 hours. In addition, this case could be considered
as one of brief psychotic disorder, because she had been
under considerable stress at the time. Prescription of aripiprazole during the outpatient follow-up period was another confounding factor, making it hard to know whether the
remission of her symptoms was due to stopping amphetamine analogue or the effect of antipsychotics. A re-challenge test with phentermine would have been the most satisfactory way to prove a definite diagnosis. However, this
was not feasible for ethical reasons.
Prescription rates for appetite suppressants are ever
increasing. However, careful consideration of their possible psychiatric side effects is often neglected. This case illustrates the sudden onset of psychotic symptoms after
Auditory hallucination,
delusion of persecution,
idea of reference,
delusion of thought
insertion
Personality change,
delusion of persecution,
depression
Auditory/visual
hallucination, idea of
reference, delusion of
persecution
Auditory hallucination,
delusion of persecution
Auditory hallucination,
delusion of persecution
Treatment/Prognosis
Relieved in 3 weeks
with chlorpromazine,
no recurrence
No recurrence in 6
months with
chlorpromazine
No recurrence in 6
months with
chlorpromzaine
Relieved in 3 days
with thioridazine
Relieved in 15 days
with trifluoperazine,
psychotic symptom
recurred in 1 week
with phetermine 90 mg
Relieved in 10 days with
haloperidol, no
recurrence
Relieved in 6 weeks with
tranylcypromine
Spontaneously relieved
in 25 days
continuous use of phentermine and rapid remission following treatment. Therefore, when prescribing amphetamine analogue to treat obesity, clinicians should warn
about possible psychiatric symptoms as side effects and
perform careful assessments of patients’ psychiatric treatment histories or vulnerabilities, if indicated. Further
studies are needed to establish a clear causal relationship
between appetite suppressants and psychotic symptoms
using more specific urine tests and long-term follow up.
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