R
Rapaport M, Braff DL.
Alprazolam and Hostility.
American Journal of Psychiatry 1985; 142: 146.

" Monoamine oxidase inhibitors suppress the REM sleep and are correlated with patient
self-reports of decreased dreaming. Recently we treated a patient who said she began having
violent sadomasochistic nightmares and the return of self-mutilatory impulses after 0.25 mg t.i.d.
of alprazolam was added to her regimen of tranylcypromine, 30 mg/day. Both the patients
sadomasochistic nightmares and her self-mutilatory impulses ceased 24 hours after her last dose of
alprazolam."

[Key words; Xanax, alprazolam, nightmares]

Regestein QR, Reich P.
Agitation Observed During Treatment with Newer Hypnotic Drugs.
Journal of Clinical Psychiatry 1985; 46: 280-283.

Side effects involving agitation, e.g. sleepwalking, anger, and panic, were observed in 10
insomniac patients treated with temazepam or triazolam but not other benzodiazepines. Each
patient described these side effects as uncharacteristic. Milder agitation was observed in 2 cases.
In 4 cases, these effects were doubted by the precribing physician. This type of side effect has
been only slowly recognised for other benzodiazepines and has not been much reported for these
newer agents. Agitation observed during treatment with these agents may be related to their short
elimination half-lives. [SUMMARY p. 280]

[Key words; Halcion, Euhypnos, Normison, triazolam, temazepam, anxiety, aggression, hostility,
paradoxical effects]

Rejent TA, Wahl KC.
Diazepam Abuse: Incidence, Rapid Screening and Confirming Methods.
Clinical Chemistry 1976; 22: 889-891.

" The abuse of drugs continues unabated in the United States. Awareness of "hard drug" use
predominates in the news media and funded programs, but the facts concerning other drug misuse
are generally hidden. Diazepam (and probably others) are heavily misused, but are not the
subject of critical editorialization."

" Highly prescribed psychotropic drugs can easily end up in the hands of many others. Therefore,
the clinical analyst should be aware of drug popularity, which in our present society leads to
overuse, abuse, and often requires medical intervention in a clinical emergency . " [p. 891]

[Key words; addiction, abuse, dependence]

Rementeria JL, Bhat K.
Withdrawal Symptoms in Neonates From Intrauterine Exposure to
Diazepam.
Journal of Pediatrics 1977; 90: 123-126.

Three infants are presented who had withdrawal symptoms after prolonged, intrauterine
exposure to diazepam. Symptoms, clinical course, management, and laboratory findings are
described. Some physiologic aspects of diazepam in the fetus and neonate are discussed. One
infant died at six weeks of age; death was attributed to the sudden infant death syndrome.
[ABSTRACT p.123]

[Key words; Valium, diazepam, dependence, withdrawal, infants, pregnancy]

Rickels K, Case WG, Schweizer EE, Swenson C, Fridman RB.
Low-Dose Dependence in Chronic Benzodiazepine Users: A Preliminary
Report on 119 Patients.
Psychopharmacology Bulletin 1986; 22: 407-415.

" In fact, one hard-earned lesson is that long-term BZ users are in need of much more intensive
psychiatric and social support than other anxious or depressed patients. " [p. 414]

[Key words; long-term effects]

Rickels K, Schweizer E, Case G, Greenblatt DJ.
Long-Term Therapeutic Use of Benzodiazepines. I. Effects of Abrupt
Discontinuation.
Archives of General Psychiatry 1990; 47: 899-907.

" Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower
levels of anxiety than before benzodiazepine discontinuation. " [p. 899]

[Key words; long-term effects, detoxification]

Rigby J, Harvey M, Davies DR.
Mania Precipitated by Benzodiazepine Withdrawal.
Acta Psychiatrica Scandinavica 1989; 79: 406-407.

A case of mania following abrupt benzodiazepine withdrawal in an 83-year-old woman is
described. It is argued that the withdrawal state acted as a significant life event in precipitating the
manic episode. [ABSTRACT p. 406]

[Key words; Ativan, lorazepam, addiction, dependence, withdrawal, mania]

Risse SC, Whitters A, Burke J, Chen S, Scurfield RM, Raskind MA.
Severe Withdrawal Symptoms after Discontinuation of Alprazolam in Eight
Patients with Combat-Induced Posttraumatic Stress Disorder.
Journal of Clinical Psychiatry 1990; 51: 206-209.

Eight patients with combat-induced posttraumatic stress disorder (PTSD) receiving long-term
alprazolam therapy for anxiety or depression (maximum dose of 2-9 mg/day for 1-5 years) had
alprazolam therapy withdrawn. Most of the patients underwent gradual medication withdrawal.
All patients had a prior history of alcohol abuse or benzodiazepine dependence. During
withdrawal, all patients had severe reactions including anxiety, sleep disturbance, rage reactions,
hyperalertness, increased nightmares, and intrusive thoughts; and 6 of the 8 patient s had
homicidal ideation. As a result of this report, the authors suggest that the potential for severe
withdrawal reactions, even with gradual tapering, should be considered before prescribing
alprazolam therapy for this group of patients. [ABSTRACT p. 206]

[Key words; Xanax, alprazolam, addiction, dependence, withdrawal, detoxification, hostility,
aggression, nightmares, insomnia]

Rivas F, Hernandez A, Cantu JM.
Acentric Craniofacial Cleft in a Newborn Female Prenatally Exposed to a
High Dose of Diazepam.
Teratology 1984; 30: 179-180.

A newborn female with craniofacial clefts, including cleft lip and palate, was studied. The mother
had ingested 580 mg of diazepam in a single dose at about the 43rd day of gestation. The
synchronism of drug intake and the embryological development of the affected structures suggests
an etiopathogenic relationship. [ABSTRACT p. 179]

[Key words; teratogenic effects, infants]

Roberts K, Vass N.
Schneiderian First-Rank Symptoms Caused by Benzodiazepine Withdrawal.
British Journal of Psychiatry 1986; 148: 593-594.

Benzodiazepine withdrawal has been found to give rise to numerous physical and psychological
symptoms. This paper describes, for the first time, Schneiderian first-rank symptoms of
schizophrenia caused by such withdrawal. [SUMMARY p. 593]

[Key words; addiction, withdrawal, abuse, dependence, withdrawal psychosis]

Roche Products Inc. Manati, Puerto Rico.
" The effectiveness of Valium in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. " [p.893]
[ In advertisement for "Valium", Archives of General Psychiatry 1990; 47: 893.]

" SIDE EFFECTS: Drowsiness, confusion, diplopia, hypotension, changes in libido, nausea,
fatigue, depression, dysarthria, jaundice, skin rash, ataxia, constipation, headache, incontinence,
changes in salivation, slurred speech, tremor, vertigo, urinary retention, blurred vision.
Paradoxical reactions such as acute hyperexcited states, anxiety, hallucinations, increased muscle
spasticity, insomnia, rage, sleep disturbances, stimulation have been reported; should these occur,
discontinue drug. "

Romney DM, Angus WR.
A Brief Review of the Effects of Diazepam on Memory.
Psychopharmacology Bulletin 1984; 20: 313-316.

" Moreover, it [i.e. diazepam] appears to produce side effects, previously unnoticed, both on
mood, causing depression and rage, and on cognitive and psychomotor functioning. " [p. 313]

[Key words; Valium, diazepam, depression, aggression, cognitive impairment, psychomotor
impairment]

Ross M.
Lorazepam-Associated Drug Dependence.
Journal of the Royal College of General Practioners 1986; February: 86.

" I should like to draw attention to what, in my opinion, are the unequivocal risks of
lorazepam-associated drug dependence and exaggerated withdrawal symptoms. In my
experience, this can occur often with low dosage, short courses and for many months after
cessation of therapy.

It is common to find other general practioners and psychiatrists who share this view and there is
also widespread lay awareness of the problem. For the last year and a half I have been
communicating with the Committee on Safety of Medicines about the problem. They answer that
they have received few yellow card reports on this problem.

My personal view is that this is because doctors do not realise that reporting an expected
side-effect of a drug is as useful for epidemiological purposes as is reporting an unexpected
side-effect for general scientific purposes. I should like, therefore, to appeal to all the general
practitioners who must be seeing this problem, to report any cases to the Committee on Safety of
Medicines. " [p. 86]

[Key words; Ativan, lorazepam, addiction, dependence, abuse, withdrawal]

Rosenbaum JF, SW Woods, Groves JE, Klerman GL.
Emergence of Hostility During Alprazolam Treatment.
American Journal of Psychiatry 1984; 141: 792-793.

Of 80 patients given alprazolam, eight became hostile early in treatment. The authors suggest that
alprazolam-induced hostility may be more likely in patients with well-suppressed chronic anger
and resentment and cite reports of hostility associated with other benzodiazepines. [SUMMARY
p. 792]

[Key words; Xanax, alprazolam, aggression, paradoxical effects]

Rowlatt RJ.
Effects of Maternal Diazepam.
BMJ 1978; 1: 985.

" High doses (30 mg or more) of diazepam administered during labour cause, in the infant, failure
to start breathing, shallow, inadequate respirations, periodic cessations of respiration, floppiness,
subnormal temperature, and poor sucking. These effects last several days and significant plasma
levels of diazepam and of its active metabolites persist for up to eight days. Diazepam
accumulates in tissue of the fetus, and is metabolised and excreted slowly by the newborn baby. "

" The depressant effects of pethidine and other drugs given during labour would be made worse
by diazepam. "

" Diazepam is excreted in breast milk, which may sedate the baby and cause feeding difficulty.
Finally, there is the fear of impairing future intellectual development by exposing the developing
brain to the influence of tranquillisers.

" How often must we be reminded of the ancient precept primum non nocere ? "
[Key words; Valium, diazepam, pregnancy, infants]

Ryan HF, Merrill FB, Scott GE, Krebs R, Thompson BL
Increase in Suicidal Thoughts and Tendencies Association with Diazepam
Therapy.
JAMA 1968; 203: 1137-1139.

Seven cases occurred in which there was an association in time between the institution of
diazepam therapy and the onset of suicidal thoughts and tendencies, which tended to be
concealed by patients who were at the time receiving psychiatric treatment.

An additional patient demonstrated deepening of depression while receiving diazepam. Physicians
should consider the possible adverse depressive effect of diazepam when prescribing it as an
antianxiety agent. [SUMMARY p. 1137]

" The major adverse side effects have been considered to be the possible development of ataxia
and confusion. However, the report by Feldman of the progressive development of dislike and
hate in some patients, manifested in one by an overt act of violence, may not be totally unrelated
to the problem to which we here address ourselves. " [p. 1137]

" There has been no clear warning that diazepam may have this kind of adverse effect in
psychiatric patients, only that it cannot be expected to do the job of the accepted antidepressants
in patients with severe depression. It would seem that caution should be exercised in the use of
diazepam in all patients in order to promptly detect adverse depressive effects. The use of
diazepam in even mild depressions, in our view, requires consideration of the potential onset of
suicidal thoughts and tendencies which may not be readily recognised. " [p. 1137]

[Key words; Valium, diazepam, depression, suicide, paradoxical effects]

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