LE1TERS
TO THE
EDITOR
of these episodes she stabbed her boyfriend She was frequently hypersexual and was have disorganized and delusional thinking.
An initial
EEG when
she was not taking
with scissors. also noted to
with
discontinuation
was
of propranotot,
she
again
began to manifest at least daily complex partial seizures. An EEG done during this period revealed only generalized slowing. The seizures persisted despite an increase in her carbamazepine level to between 10 and 14 igimh, achieved
by increasing on propnanolol, again over the free over the resume taking
the dose
to 600
mg t.i.d.
She was
restarted
120 mg b.i.d., and her condition stabilized course of 3 days. She has remained seizure subsequent month and has been able to canbamazepine twice a day.
We believe that in this patient, the combination of propranohol and carbamazepine may have produced a synergistic anticonvulsant effect. While it is possible that these medications did not exert their effects on seizure activity, our
clinical
observations
suggest
that
relevance to the treatment of some matic organic brain syndromes or dens (5).
they
did.
patients refractory
as an Adjunct
SIR: Benzodiazepine
medication
normal, and three subsequent EEGs when she was taking medication were notable primarily for generalized slowing. CT and magnetic resonance imaging revealed minimal asymmetry of temporal horn size, the right being greater than the left, but both scans were otherwise unremarkable. Neuropsychological testing was performed on three separate occasions over a S-year period and each time revealed diffuse cerebral dysfunction. Oven the course of several prolonged hospitalizations, Ms. A’s condition was stabilized with a combination of fluphenazine, S mg b.i.d.; benztropine, 1 mg b.i.d.; lithium carbonate, 600 mg b.i.d.; carbamazepine, 400 mg b.i.d.; and propranolol, 120 mg b.i.d. Carbamazepine levels were in the range of 5-8 ig/ml, and the patient was without clinical seizures or violent episodes for 8 months. However, because of her hypercholesterotemia, an attempt was made to taper Ms. A’s dose of propranolol. This was done over a 2-week period without evidence of rebound hypertension while she was in the hospital. Co-
incident
Phenobarbital
This
may
be of
with posttrauseizure disor-
REFERENCES 1. Fischer
W, Muller M: Pharmacological modulation of central monoaminergic systems and influence on the anticonvulsant effectiveness in maximal electroshock seizure. Biomed Biochim Acta 1988; 47:631-645 2. Jaeger V, Esplin B, Capek R: The anticonvulsant effects of propranolot and beta-adrenergic blockade. Experientia 1979; 35: 80-81
3. Williams D: The structure of emotions reflected in epileptic experiences. Brain 19S6; 79:29-67 4. Theodore WH, Porter RJ, Penry JK: Complex partial seizures: clinical characteristics and differential diagnosis. Neurology 1983; 33:1115-1121 S. Bouvy PF, van de Wetering BJM, Meerwaldt JD, et at: A case of organic brain syndrome following head injury successfully treated with carbamazepine. Acta Psychiatr Scand 1988; 77: 361-363
for Alprazolam
withdrawal
symptoms have been well discontinuation studies of persons receiving shortor long-term benzodiazepine therapy. Withdrawal symptoms were noted in six of nine short-term studies and in seven of nine long-term studies. Alprazolam withdrawal can be problematic. A multicenter trial of alprazotam for panic disorder and agoraphobia (2) described withdrawal symptoms in 35% of the subjects. Tapering the dose of ahprazotam may take up to 8 weeks (2).
documented.
Noyes
Clonazepam
(3) and chonidine
a safer
et at. (1) reviewed
(4) have
been
used to provide
is cross-tolerant with agents (5). We report
ethyl
alcohol
withdrawal
regimen.
Phenobarbital sedative hypnotic ful alprazoham
withdrawal
with
F. RENSHAW, M.D., PH.D. HARRY E. FORD, M.D. ANDREW W. BROTMAN, M.D. Boston, Mass.
1688
and the
two cases of successuse of phenobarbital.
the
Ms. A, a 51-year-old woman, had a 3-year history of migraine-like headaches attributed to the onset of fibromyositis and had been treated for 3 years with alprazolam, 13 mg/day, and doxepin, 100 mg at bedtime. She was hospitalized for ahprazoham withdrawal. She was placed on a regimen of atprazolam, 1 1 mg/day, on hospital day 2, along with phenobarbital, 120 mg/day. The alprazolam
was tapered by means of a 2-mg decrease the last dose was given on hospital day
every third day; 24. She was pre-
scribed phenobarbital, 90 mg/day for days 2 through 25, 60 mg/day for days 26 and 27, and 30 mg/day for days 28 and 29. Doxepin, 100 mg, was continued throughout the hospital stay. Her vital signs remained stable, and she cxhibited no signs or symptoms of withdrawal. She was discharged from the hospital on day 30. Ms. B, a 33-year-old woman, had a 1-year history of back pain. She was prescribed alprazolam and a combination of propoxyphene, 100 mg, and acetaminophen, 650 mg. She gradually increased the alprazolam to 15-20 mg/ day and the propoxyphene-acetaminophen to 20-30 tab-
lets/day. as she
She was
hospitalized
180
was
abusing
her
for supervised
withdrawal,
drugs. Opioid withdrawal was treated with clonidine, 0.1 mg on hospital day 1, 0.2 mg on day 2, 0.3 mg on day 3, and 0.2 mg on day 4. Alprazolam was tapered as follows: 8 mg on day 1, 12 mg on days 2 and 3, 9 mg on days S through 10, 7.5 mg on days 11 through 13, 4.5 mg on days 14 through 16, 3 mg on days 17 through 19, 1.5 mg on days 20 through 22, 1 mg on day 23, and 0.5 mg on day 24. The phenobarbital
regimen
was
prescription
120 mg on days
mg on days
20 through
1 through 22 due
19, an increase
to the
patient’s
to
report
of mild withdrawal symptoms, and 90 mg on days 23 and 24. She heft the hospital on the 25th day because her husband was arrested her children.
and
Both patients had mate medical illnesses.
patient aches. with
needed
been started Alprazotam
to go home
to care
on alprazolam was increased
the use of phenobarbital.
The
patient
had
for
for legitifor the first
by her physician in an attempt to control Alprazolam withdrawal was accomplished
hospital The
she
her headin 30 days
an uneventful
course. second
patient
increased
propoxyphene-acetaminophen. PERRY
Withdrawal
her doses
When
of alprazolam
she
developed
drawal symptoms on day 20, an increase in the bital dose led to relief of her symptoms. Psychiatrists will need to develop and implement to detoxify patients from psychoactive substances
Am
J
Psychiatry
147:12,
December
and
with-
phenobarstrategies in a safe,
1990
LETTERS
timely
manner.
ing with
Phenobarbital
the
complex
appears
problem
to have promise
of alprazotam
in deal-
withdrawal.
REFERENCES
1. Noyes R Jr, Garvey
a review 382-389 Pecknold JC, Swinson RP, Kuch K, et at: Alprazolam in panic disorder and agoraphobia: results from a mutticenter trial. Arch Gen Psychiatry 1988; 45:429-436 Patterson JF: Alprazolam dependency: use of clonazepam for withdrawal. South Med J 1988; 8 1:830-836 Fyer AJ, Liebowitz MR, Gorman JM, et at: Effects of clonidine on atprazolam discontinuation in panic patients: a pilot study. J Chin Psychopharmacol 1988; 8:270-274 Smith DE, Wesson DR: A new method for treating barbiturate dependence. JAMA 1970; 213:294-295 drawal:
2.
3. 4.
5.
MJ, Cook BL, et at: Benzodiazepine withof the evidence. J Clin Psychiatry 1988; 49:
RONALD W. MCNICHOL, KENNETH N. VOGTSBERGER, WILLIAM A. ZULE, San Antonio,
Survivable
Fluvoxamine
SIR: Fluvoxamine ethyloximethers uptake
M.D. M.D. B.A. Tex.
Overdose
is a compound of aralkylketones
of serotonin
without
in the series that inhibits
noradrenergic,
of 2-aminoneuronal re-
monoamine
ox-
idase, amphetamine, or anticholinergic effect. Metabolism is by oxidation of the methoxyl group. The mean plasma halflife is 15 hours after a single dose in healthy volunteers (1). Fluvoxamine is structurally similar to fluoxetine, another serotonergic antidepressant. Neither agent causes arrhythmias, the usual cause of death after tricychic overdose.
In patients taking changes in heart rate
this drug, no or blood pressure
clinically important have been observed.
fluvoxamine
had
plus
bromazepam,
convulsions
gested
3.0
g of
temazepam vascular which
and
and
Another
elderly
recovered.
fluvoxamine,
tablets,
death a patient
Imodium,
which
60
oxazepam
resulted
in CNS
or ECG
5.0 whiskey.
g of She
woman
in-
tablets,
and
but
cardio-
not
30
(1). I would like to report a case of my own took an overdose of fluvoxamine.
Ms. A, a 31-year-old woman with cyclic hypomania and depression (bipolar II), began a blind trial of placebo, desipramine, or fluvoxamine. During placebo washout, irritabihity, agitation, and insomnia were noted, but the study medication was increased to 150 mg/day, with timely re-
mission patient
of depressive symptoms. Six months impulsively took 4.8 g of fluvoxamine,
amitniptyhine, and 7 g of naproxen. produced return of pill fragments.
an intensive mia.
She
care was
unit
and showed
dystaxic
and
consciousness and she noted toms from the amitriptyhine. diverticuhum
Am
J
Psychiatry
and
required
147:12,
Lavage She was
hater, 0.75 1 hour monitored
no evidence
somnolent,
but
December
1990
later in
of arrhythshe
never
marked antichotinergic She suffered a ruptured a hemicolectomy.
this g of
lost
sympcecal
stopped. One month after fast speech, mild euphoria,
the overextreme
Fluvoxamine may be capable of precipitating mania, as is the analogue fluoxetine (2-4). Perse et al. (5) reported mania in a woman with obsessive-compulsive disorder and bipolar affective disorder who was treated with fluvoxamine. Investigators should be aware of the potential switch effect of this drug, which, hike fluoxetine, appears nonlethal in massive overdose.
REFERENCES 1 . Summary of the Properties of Fluvoxamine Maleate. Edited by Duin HGJ, Tijsma C. Weesp, The Netherlands, Duphar, March 1986 2. Settle EC Jr. Settle GP: A case of mania associated with fluoxetine. Am J Psychiatry 1984; 141:280-28 1 3. Chouinard G, Steiner W: A case of mania induced by high-dose fluoxetine treatment (letter). Am J Psychiatry 1986; 143:686 4. Lebegue B: Mania precipitated by fluoxetine (letter). Am J Psychiatry 1987; 144:1620 S. Perse TL, Greist JH, Jefferson JW, et at: Fluvoxamine treatment of obsessive-compulsive disorder. Am J Psychiatry 1987; 144: 1543-1548
BRECK
LEBEGUE,
Salt Lake
Bupropion
effect been
and
greater than to the drug’s
City,
M.D. Utah
Delirium
Bupropion,
profile, associated
an
has
antidepressant
with
recently become with bupropion
a favorable
available. Psychosis (1), particularly at
450 mg/day. The psychosis dopamine-reuptake-btocking
tion is advised when using L-dopa cians’ Desk Reference). We report delirium associated with concurrent
is most activity,
side has doses
likely due and cau(Physi-
with bupropion the appearance of acute use of bupropion and
amantadine. Mr. A, a 75-year-old kinsonism
developed in
EDITOR
insomnia, increased energy, marked mood lability, pressure of speech, and hypergraphia. This episode was much more severe than her hypomanic episodes before fluvoxamine use. Administration of lithium carbonate led to euthymic mood in a few weeks.
SIR:
Nausea, constipation, and somnolence are the usual symptoms that emerge. The drug is currently marketed in several European countries and is under clinical investigation in the United States. Two cases of massive overdose of fluvoxamine alone (4.8 g and 3.0 g) have been reported (unpublished); both patients
fully recovered. There were no abnormal laboratory findings in these cases (1). A third patient ingested
Fluvoxamine was dose, Ms. A exhibited
TO THE
(for
man
which
depressive
he
with moderate idiopathic parwas treated with amantadine),
symptoms
and paranoid
ideation
18
months before hospitalization. His paranoia was refractory to haloperidol, and he could not tolerate tnicychic antidepressants. Daily function was good despite these probhems until 6 months before hospitalization, when his condition worsened, prompting admission. On admission, Mr. A complained of depressed mood and displayed vegetative symptoms, psychomotor retardation, and nihilistic delusions. Results of a physical examination were unremarkable; neurological examination
showed tremor. ECT
significant rigidity, festinating gait, and resting Findings of a laboratory evaluation were normal. was
initiated
no contraindications.
after
a pretreatment
Seven
biweekly
work-up
unilateral
revealed
(nondom-
inant) ECTs resulted in marked improvement of the depressive and parkinsonian symptoms; no significant confusion or memory changes were noted. After ECT, bupropion, 75 mg b.i.d., was added; other medications
1689