Lorazepam - Wikipedia, the free encyclopedia http://en.wikipedia.

org/wiki/Ativan

From Wikipedia, the free encyclopedia

(Redirected from Ativan)

Lorazepam, initially marketed under the brand names Ativan

and Temesta, is a benzodiazepine drug with short to medium
duration of action. It has all five intrinsic benzodiazepine
effects: anxiolytic, amnesic, sedative/hypnotic,
anticonvulsant and muscle relaxant.[4] It is a powerful
anxiolytic, and, since its introduction in 1977, lorazepam's
principal use has been in treating the symptom of anxiety.
Among benzodiazepines, lorazepam has a relatively high
addictive potential.[5]

1 Uses
2 Formulation and administration
3 Adverse effects
4 Contraindications and special considerations
4.1 Contraindications
4.2 Special groups and situations
4.3 Tolerance and dependence
4.3.1 Withdrawal Lorazepam
5 Pharmacology Systematic (IUPAC) name
5.1 Pharmacokinetics
(RS)-9-chloro-6-(2-chlorophenyl)-4-hydroxy-
5.2 Pharmacodynamics
2,5-diazabicyclo[5.4.0]undeca-
6 Interactions 5,8,10,12-tetraen-3-one
7 Overdose
8 Abuse and misuse Identifiers
9 History and legal status CAS number 846-49-1
10 In popular culture ATC code N05BA06
11 See also
12 References PubChem 3958
13 External links DrugBank APRD00116
ChemSpider 3821
Chemical data
Formula C15H10Cl2N2O2
Mol. mass 321.2 g/mol
Pharmacokinetic data
Bioavailability 85% of oral dose

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Lorazepam has relatively potent anxiolytic effects and its

best known indication is the short-term management of Metabolism Hepatic glucuronidation
severe chronic anxiety, though in fact the FDA advises Half life 9–16 hours[1][2][3]
against this usage.[6] It is fast acting, and useful in treating Excretion Renal
fast onset panic anxiety.[7] Therapeutic considerations
Lorazepam has strong sedative/hypnotic effects, and the Pregnancy cat.
D(US)
duration of clinical effects from a single dose makes it an
appropriate choice for the short term treatment of insomnia,
Legal status
particularly in the presence of severe anxiety. Withdrawal Schedule IV(CA) Class C(UK)
symptoms, including rebound insomnia and rebound anxiety, Schedule IV(US)
may occur after only 7 days' administration of lorazepam.[8]
Routes Oral, I.M., I.V. and transdermal
[4]
Its relatively potent amnesic effect, with its anxiolytic and (what is this?) (verify) (http://en.wikipedia.org
sedative effects, makes lorazepam useful as premedication. It /w/index.php?&diff=cur&oldid=307815814)
is given before a general anaesthetic to reduce the amount of
anaesthetic agent required, or before unpleasant awake procedures, such as
in dentistry or endoscopies, to reduce anxiety, to increase compliance, and
to induce amnesia for the procedure. Oral lorazepam is given 90 to 120
minutes before procedures, and intravenous lorazepam as late as 10 minutes
before procedures.[9][10][11]

The marked anticonvulsant properties of lorazepam, and its

pharmacokinetic profile, makes intravenous lorazepam a reliable agent for
terminating acute seizures, but it has relatively prolonged sedation
aftereffects. Oral lorazepam, and other benzodiazepines, have a role in
long-term prophylactic treatment of resistant forms of petit mal epilepsy but
not as first-line therapies, mainly because of the development of resistance
to their effects.[12]

Lorazepam's anticonvulsant, or CNS depressant, properties are useful for

the prevention and treatment of alcohol withdrawal syndrome. In this 1987 Ativan advertisement. "In a
world where certainties are
setting it is relevant that impaired liver function is not a hazard with
few...no wonder Ativan
lorazepam since lorazepam does not require oxidation, hepatic or otherwise, (lorazepam)C-IV is prescribed by
for its metabolism.[13][14] so many caring clinicians."

Where there is need for rapid sedation of violent or agitated patients,[15][16]

including acute delirium, lorazepam may be used, but as it can cause paradoxical effects, it is preferably given
together with haloperidol.[17] Lorazepam is absorbed relatively slowly if given intramuscularly, a common route
in restraint situations.

Catatonia with inability to speak is responsive and sometimes controlled with a single 2 mg oral, or slow
intravenous, dose of lorazepam. Symptoms may recur and treatment for some days may be necessary. Catatonia
due to abrupt or too rapid withdrawal from benzodiazepines, as part of the benzodiazepine withdrawal
syndrome, should also respond to lorazepam treatment.[18] As lorazepam can have paradoxical effects,
haloperidol is sometimes given concomitantly.[17][19]

It is sometimes used in chemotherapy as an adjunct to antiemetics for treating anticipatory nausea and vomiting,
i.e. nausea and vomiting caused or worsened by psychological sensitisation to the thought of being sick.[20] It is

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also used as adjunct therapy for cyclic vomiting syndrome.

Pure lorazepam is an almost white powder that is nearly insoluble in water and
oil. In medicinal form, lorazepam is mainly available as tablets and a solution
for injection but in some locations it is also available as a skin patch, an oral
solution and a sublingual tablet.

Lorazepam tablets and syrups are administered by mouth only. The tablets
contain 0.5 mg, 1 mg, or 2 mg lorazepam, with some differences between
countries. Lorazepam tablets of the Ativan brand also contain lactose,
microcrystalline cellulose, polacrilin potassium, magnesium stearate and
colouring agents (indigo carmine—E132—in blue tablets and tartrazine
—E102— in yellow tablets).
0.5mg tablets of the Ativan
Lorazepam injectable solution is administered either by deep intramuscular brand of lorazepam.
injection or by intravenous injection. The injectable solution comes in 1 mL
ampoules containing 2 mg or 4 mg lorazepam. The solvents used are
polyethylene glycol 400 and propylene glycol. As a preservative, the injectable solution contains benzyl
alcohol.[21] Toxicity from propylene glycol has been reported in the case of a patient receiving a continuous
lorazepam infusion.[22] Intravenous injections should be given slowly and patients closely monitored for
side-effects, such as respiratory depression, hypotension, or loss of airway control.

Peak effects roughly coincide with peak serum levels,[23] which occur 10 minutes after intravenous injection, up
to 60 minutes after intramuscular injection, and 90 to 120 minutes after oral administration,[23][24] but initial
effects will be noted before this. A clinically relevant lorazepam dose will normally be effective for 6 to 12
hours, making it unsuitable for regular once-daily administration, so it is usually prescribed as two to four daily
doses when taken regularly.

Any of the five intrinsic benzodiazepine effects possessed by lorazepam (sedative/hypnotic, muscle relaxant,
anxiolytic, amnesic and anticonvulsant) may be considered as "adverse effects," or "side-effects," if
unwanted.[4] Lorazepam's effects are dose-dependent, meaning that the higher the dose the stronger the effects
(and side-effects) will be. Using the smallest dose needed to achieve desired effects lessens the risk of adverse
effects.

Sedation is the most complained-of side-effect. In a group of around 3500 patients treated for anxiety, the most
common side-effects complained of from lorazepam were sedation (15.9%), dizziness (6.9%), weakness (4.2%),
and unsteadiness (3.4%). Side-effects such as sedation and unsteadiness increased with age.[25]

Paradoxical effects: In some cases there can be paradoxical effects with benzodiazepines, such as
increased hostility, aggression, angry outbursts, and psychomotor agitation.[26] Paradoxical effects are
more likely to occur with higher doses, in patients with pre-existing personality disorders and those with a
psychiatric illness. It is worth noting that frustrating stimuli may trigger such reactions, even though the
drug may have been prescribed to help the patient cope with such stress and frustration in the first place.
As paradoxical effects appear to be dose related, they usually subside on dose reduction or on complete

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withdrawal of lorazepam.[27][28][29][30][31][32]

Suicidality: Benzodiazepines may sometimes unmask suicidal ideation in depressed patients, possibly
through disinhibition or fear-reduction. Though relatively non-toxic in themselves, the concern is that
benzodiazepines may inadvertently become facilitators of suicidal behaviour.[33] Lorazepam should,
therefore, not be prescribed in high doses or as the sole treatment in depression but only together with an
appropriate antidepressant.

Amnesic effects: Among benzodiazepines, lorazepam has relatively strong amnesic effects,[4][34] but
patients soon develop tolerance to this with regular use. To avoid amnesia (or excess sedation) being a
problem, the initial total daily lorazepam dose should not exceed 2 mg. This also applies to use for night
sedation. Five participants in a sleep study were prescribed lorazepam 4 mg at night, and the next evening
three subjects unexpectedly volunteered memory gaps for parts of that day, an effect that subsided
completely after 2–3 days' use.[35] Amnesic effects cannot be estimated from the degree of sedation
present, since the two effects are unrelated.

Full lists of Lorazepam side-effects:

For lists of lorazepam side-effects, refer to the manufacturers' data sheets. Please note that some may list
side-effects for the entire benzodiazepine class, not the specific side-effect profile for lorazepam.

Contraindications

Lorazepam must be avoided in patients with the following conditions:

Allergy or hypersensitivity. Past hypersensitivity or allergy to lorazepam, to any benzodiazepine or to

any of the ingredients in lorazepam tablets or injections.

Severe respiratory failure. Benzodiazepines, including lorazepam, may depress central nervous system
respiratory drive and are contraindicated in severe respiratory failure. An example would be the
inappropriate use to relieve anxiety associated with acute severe asthma. The anxiolytic effects may also
be detrimental to a patient's willingness and ability to fight for breath. However, if mechanical ventilation
becomes necessary, lorazepam may be used to facilitate deep sedation.

Acute intoxication. Lorazepam may interact synergistically with the effects of alcohol, narcotics, or
other psychoactive substances. It should, therefore not be administered to a drunk or intoxicated person.

Ataxia. This is a neurological clinical sign, consisting of unsteady and clumsy motion of the limbs and
torso, due to failure of gross muscle movement coordination, most evident on standing and walking: It is
the classic way in which acute alcohol intoxication may affect a person. Benzodiazepines should not be
administered to already-ataxic patients.

Acute narrow-angle glaucoma. Lorazepam has pupil-dilating effects, which may further interfere with
the drainage of aqueous humour from the anterior chamber of the eye, thus worsening narrow-angle
glaucoma.

Sleep apnea. Sleep apnea may be worsened by lorazepam's central nervous system depressant effects. It
may further reduce the patient's ability to protect his or her airway during sleep.

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Myasthenia gravis. This condition is characterised by muscle weakness and a muscle relaxant such as
lorazepam may exacerbate symptoms.

Pregnancy and breast feeding. Lorazepam belongs to the Food and Drug Administration (FDA)
pregnancy category D, which means that it is likely to cause harm to the developing baby, if taken during
the first trimester of pregnancy. There is inconclusive evidence that lorazepam, if taken early in
pregnancy, may result in reduced IQ, neurodevelopmental problems, physical malformations in cardiac or
facial structure, as well as other malformations in some newborns. Lorazepam given to pregnant women
antenatally may cause floppy infant syndrome[36] in the neonate, or respiratory depression necessitating
ventilation. Regular lorazepam use during late pregnancy (the third trimester), carries a definite risk of
benzodiazepine withdrawal syndrome in the neonate. Neonatal benzodiazepine withdrawal may include
hypotonia, reluctance to suck, apneic spells, cyanosis, and impaired metabolic responses to cold stress.
Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been
reported to persist from hours to months after birth.[37] Lorazepam may also inhibit foetal liver bilirubin
glucuronidation, leading to neonatal jaundice. Lorazepam is present in breast milk, so caution must be
exercised about breast feeding.

Special groups and situations

Children and the elderly. The safety and effectiveness of lorazepam is not well determined in children
under 16 years of age, but it is used to treat serial seizures. Dose requirements have to be individualized,
especially in the elderly and debilitated patients in whom the risk of oversedation is greater. Long term
therapy may lead to cognitive deficits, especially in the elderly, but this is reversible after a period of
discontinuation. Benzodiazepines, including lorazepam, have been found to increase the risk of falls and
fractures in the elderly.[38]

Liver or Kidney failure. Lorazepam may be safer than most benzodiazepines in patients with impaired
liver function. Like oxazepam, it does not require hepatic oxidation, but only hepatic glucuronidation into
lorazepam-glucuronide. Therefore, impaired liver function is unlikely to result in lorazepam accumulation
to an extent causing adverse reactions.[13] Lorazepam-glucuronide and a small amount of unchanged
lorazepam are excreted by the kidneys, so in renal failure small increases in lorazepam levels may
theoretically occur.

Surgical Premedication. Informed consent that was given only after receiving lorazepam premedication
could have its validity challenged later. Staff must use chaperones to guard against allegations of abuse
during treatment. Such allegations may arise because of incomplete amnesia, disinhibition, and impaired
ability to process cues. Because of its relative long duration of residual effects (sedation, ataxia,
hypotension and amnesia), lorazepam premedication is best suited for hospital inpatient use. Patients
should not be discharged from hospital within 24 hours of receiving lorazepam premedication, unless
accompanied by a caregiver. They should also not drive, operate machinery, or use alcohol within this
period.

Tolerance and dependence

Tolerance to benzodiazepine effects develops with regular use. This is desirable with amnesic and sedative
effects, undesirable with anxiolytic, hypnotic, and anticonvulsant effects. Patients at first experience drastic
relief from anxiety and sleeplessness, but symptoms gradually return, relatively soon in the case of insomnia but
more slowly in the case of anxiety symptoms. After four to six months of regular benzodiazepine use, there is
little evidence of continued efficacy. If regular treatment is continued for longer than this, dose increases may
be necessary to maintain effects, but treatment resistant symptoms may in fact be benzodiazepine withdrawal

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symptoms.[39]

On abrupt, or overly rapid discontinuation of lorazepam, anxiety and signs of physical withdrawal have been
observed, similar to those seen on withdrawal from alcohol and barbiturates. Lorazepam as with other
benzodiazepine drugs can cause physical dependence, addiction and what is known as the benzodiazepine
withdrawal syndrome. The higher the dose and the longer the drug is taken for the greater the risk of
experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can, however, occur from standard
dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible via
a slow and gradual dose reduction regimen.[40]

The likelihood of dependence is relatively high with lorazepam compared to other benzodiazepines. Lorazepam's
relatively short serum half-life, its confinement mainly to the vascular space, and its inactive metabolite results
in interdose withdrawal phenomena and next-dose cravings. This may reinforce psychological dependence.
Because of its high potency, the smallest lorazepam tablet strength of 0.5 mg is also a significant dose reduction
(in the UK, the smallest tablet strength is 1.0 mg, which further accentuates this difficulty). To minimise the risk
of physical/psychological dependence, lorazepam is best used only short-term, at the smallest effective dose. If
any benzodiazepine has been used long-term, the recommendation is a gradual dose taper over a period of
weeks, months or longer, according to dose and duration of use, degree of dependence and the individual.
Coming off long-term lorazepam may be more realistically achieved by a gradual switch to an equivalent dose of
diazepam, a period of stabilization on this and only then initiating dose reductions. The advantage of switching
to diazepam is that dose reductions are felt less acutely, because of the longer half lives (20–200 hours) of
diazepam and its active metabolites.[41]

Withdrawal

Withdrawal symptoms can occur after taking therapeutic doses of Ativan for as little as one week. Withdrawal
symptoms include headaches, anxiety, tension, depression, insomnia, restlessness, confusion, irritability,
sweating, dysphoria, dizziness, derealization, depersonalization, numbness/tingling of extremities,
hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhea, appetite loss,
hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panic
attacks, short-term memory loss, and hyperthermia. It takes approximately 18–36 hours for the benzodiazepine
to remove itself from your body.[42] The ease of addiction to Lorazepam, (the Ativan brand was particularly
cited), and its withdrawal were brought to the attention of the British public during the early 1980s in Esther
Rantzen's BBC TV series "That's Life!", in a feature on the drug over a number of episodes.

Lorazepam is high-potency and an intermediate-acting benzodiazepine and its uniqueness,[43][44] advantages

and disadvantages are largely explained by its pharmacokinetic properties (poor water and lipid solubility, high
protein binding and non-oxidative metabolism to a pharmacologically inactive glucuronide form) and by its high
relative potency (lorazepam 1 mg is equal in effect to diazepam 10 mg).[45][46] The half life of lorazepam is
10–20 hours.[47]

Pharmacokinetics

Because of its poor lipid solubility lorazepam is absorbed relatively slowly by mouth and is unsuitable for rectal
administration. But its poor lipid solubility and high degree of protein binding (85-90%[24]) mean that
lorazepam's volume of distribution is mainly the vascular compartment, causing relatively prolonged peak

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effects. This contrasts with the highly lipid-soluble diazepam which, although rapidly absorbed orally or rectally,
soon redistributes from the serum to other parts of the body, particularly body fat. This explains why one
lorazepam dose, despite lorazepam's shorter serum half-life, has more prolonged peak effects than an equivalent
diazepam dose.[48] On regular administration diazepam will however accumulate more, since it has a longer
half-life and active metabolites with even longer half-lives.

Clinical Example: Diazepam has long been a drug of choice for status epilepticus: Its high lipid solubility
means it gets absorbed with equal speed whether given intravenously, orally, or rectally (non-intravenous
routes are convenient in non-hospital settings). But diazepam's high lipid solubility also means it does not
remain in the vascular space but soon redistributes into other body tissues. So it may be necessary to
repeat diazepam doses to maintain peak anticonvulsant effects, resulting in excess body accumulation.
Lorazepam is the opposite case: Its low lipid solubility makes it relatively slowly absorbed by any route
other than intravenously, but once injected will not get significantly redistributed beyond the vascular
space. Therefore, lorazepam's anticonvulsant effects are more durable, thus reducing the need for
repeated doses. If a patient is known to usually stop convulsing after only one or two diazepam doses,
diazepam may be preferable because sedative after-effects will be less than if a single dose of lorazepam
is given (diazepam anticonvulsant/sedative effects wear off after 15–30 minutes, but lorazepam effects
last 12–24 hours).[49] The prolonged sedation from lorazepam may, however, be an acceptable trade-off
for its reliable duration of effects, particularly if the patient needs to be transferred to another facility.
Although lorazepam is not necessarily better than diazepam at initially terminating seizures,[50] lorazepam
is, nevertheless, replacing diazepam as the intravenous agent of choice in status epilepticus.[51][52]

Lorazepam serum levels are proportional to the dose administered. Giving 2 mg oral lorazepam will result in a
peak total serum lorazepam level of around 20 nanograms/ml around two hours later,[23][24] half of which is
lorazepam, half its inactive metabolite, lorazepam-glucuronide.[53] A similar lorazepam dose given intravenously
will result in an earlier and higher peak serum level, with a higher relative proportion of unmetabolised (active)
lorazepam.[54] On regular administration, maximum lorazepam serum levels are attained after three days.
Longer term use, up to six months, does not result in further accumulation.[24] On discontinuation, lorazepam
serum levels become negligible after 3 days and undetectable after about a week. Lorazepam is metabolised in
the liver by conjugation into inactive lorazepam-glucuronide. This metabolism does not involve hepatic
oxidation and therefore is relatively unaffected by reduced liver function. Lorazepam-glucuronide is more
water-soluble than its precursor and therefore gets more widely distributed in the body leading to a longer
half-life than lorazepam. Lorazepam-glucuronide is eventually excreted by the kidneys[24] and because of its
tissue accumulation it remains detectable - particularly in the urine - for substantially longer than lorazepam.

Pharmacodynamics

Relative to other benzodiazepines, lorazepam is thought to have high affinity for GABA receptors,[55] which
may also explain its marked[4] amnesic effects. The main pharmacological effects of lorazepam are the
enhancement of GABA at the GABAA receptor.[56] Benzodiazepine drugs including lorazepam increase the
inhibitory processes in the cerebral cortex.[57]

The magnitude and duration of lorazepam effects are dose related, meaning that larger doses have stronger and
longer-lasting effects. This is because the brain has spare benzodiazepine drug receptor capacity, with single,
clinical doses leading only to an occupancy of some 3% of the available receptors.[58]

The anticonvulsant properties of lorazepam and other benzodiazepines may be, in part or entirely, due to binding
to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to

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get limited, by the benzodiazepine effect of slowing recovery of sodium channels from inactivation in mouse
spinal cord cell cultures.[59]

Alcohol. Lorazepam is not usually fatal in overdose, but may cause fatal respiratory depression if taken in
overdose with alcohol. The combination also causes synergistic enhancement of the disinhibitory and
amnesic effects of both drugs, with potentially embarrassing or criminal consequences. Some experts
advise patients should be warned against taking alcohol while on lorazepam treatment,[4][60] but such
clear warnings are not universal.[61]

See also: Benzodiazepine overdose

In cases of a suspected lorazepam overdose, it is important to establish if the patient is a regular user of
lorazepam or other benzodiazepines, since regular use causes tolerance to develop. Also, one must ascertain if
other drugs were also ingested.

Signs of overdose range through mental confusion, dysarthria, paradoxical reactions, drowsiness, hypotonia,
ataxia, hypotension, hypnotic state, coma, cardiovascular depression, respiratory depression, and death.

Early management of alert patients includes emetics, gastric lavage, and activated charcoal. Otherwise,
management is by observation, including of vital signs, support and — only if necessary, considering the hazards
of doing so, giving intravenous flumazenil.

Patients are ideally nursed in a kind, non-frustrating environment since, when given or taken in high doses,
benzodiazepines are more likely to cause paradoxical reactions. If shown sympathy, even quite crudely feigned,
patients may respond solicitously, but they may respond with disproportionate aggression to frustrating cues.[62]
Opportunistic counseling has limited value here, as the patient is unlikely to recall this later, owing to
drug-induced anterograde amnesia.

See also: Benzodiazepine drug misuse

Lorazepam is a drug with the potential for misuse. Two types of drug misuse can occur. Recreational misuse,
where the drug is taken to achieve a "high," or when the drug is continued long term against medical advice.[63]
Prescribers of lorazepam must be alert to the possibility of abuse or diversion for illegitimate use when
prescribing for unsupervised outpatients. This applies particularly to patients with past or present substance
abuse disorders, as persons with addictive personalities are more likely to abuse medications such as lorazepam.
In addition to recreational use, benzodiazepines may be diverted and used to facilitate crime: Criminals may
take them to deliberately seek disinhibition before committing crimes[30] (which increases their potential for
violence) or they may give them to unwitting victims as date rape drugs, notably with alcohol.

In Northern Ireland in cases where drivers had low or no alcohol readings but were thought to be impaired
through drugs, benzodiazepines were found to be present in 87% of cases.[64]

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A large-scale, nationwide, U.S. government study of pharmaceutical-related ED visits by SAMHSA found that
sedative-hypnotics in the United States are the most frequently abused pharmaceuticals, with 35% of
drug-related emergency room visits involving sedative-hypnotics. In this category, benzodiazepines are most
commonly abused. Males abuse benzodiazepines as commonly as women. Of drugs used in attempted suicide,
benzodiazepines are the most commonly used pharmaceutical drug, with 26% of attempted suicides involving
benzodiazepines. Lorazepam was the third most commonly abused benzodiazepine in these ED visit
statistics.[65]

Historically, lorazepam is one of the "classical" benzodiazepines. Other

classical benzodiazepines include diazepam, clonazepam, oxazepam,
nitrazepam, flurazepam, bromazepam and clorazepate.[66] Lorazepam was first
introduced by Wyeth Pharmaceuticals in 1971 under the brand names of
Ativan and Temesta.[67] The drug was developed by President of Research,
D.J. Richards. Wyeth's original patent on lorazepam is expired in the United
States but the drug continues to be commercially viable. As a measure of its
ongoing success, it has been marketed under more than seventy generic brands
since then:

Almazine, Alzapam, Anxiedin, Anxira, Anzepam, Aplacasse, Aplacassee,

Apo-Lorazepam, Aripax, Azurogen, Bonatranquan, Bonton, Control, Donix,
Duralozam, Efasedan, Emotion, Emotival, Idalprem, Kalmalin, Larpose,
Laubeel, Lopam, Lorabenz, Loram, Lorans, Lorapam, Lorat, Lorax, Lorazene,
Lorazep, Lorazepam, Lorazin, Lorafen (PL), Lorazon, Lorenin, Loridem, Early lorazepam marketing, a
Lorivan, Lorsedal, Lorzem, Lozepam, Merlit, Nervistop L, Nervistopl, NIC, 1977 direct-to-patient
Novhepar, Novolorazem, Orfidal, Piralone, Placidia, Placinoral, Punktyl, advertisement implying its
Quait, Renaquil, Rocosgen, Securit, Sedarkey, Sedatival, Sedizepan, Sidenar, positive effects: "Now it can be
Silence, Sinestron, Somnium, Stapam, Tavor, Titus, Tolid, Tranqil, yours - The Ativan Experience."
Tranqipam, Trapax, Trapaxm, Trapex, Upan, Wintin and Wypax.

In 2000, the U.S. drug company Mylan agreed to pay $147 million to settle accusations by the F.T.C. that they
had raised the price of generic lorazepam by 2600 percent and generic clorazepate by 3200 percent in 1998
after having obtained exclusive licensing agreements for certain ingredients.[68]

Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S. and internationally under the
United Nations Convention on Psychotropic Substances.[69] Lorazepam is a Schedule IV drug under the
Controlled Drugs and Substances Act in Canada. In the United Kingdom, lorazepam is a Class C, Schedule 4
Controlled Drug under the Misuse of Drugs Regulations 2001.[70]

Lorazepam has been mentioned in several contemporary media in recent years, with various clinical aspects
highlighted. It is seen in medical situations, such as the TV series House, MD as the drug of choice for the
cessation of seizures. Usage for seizures is also depicted in the movie Saw III where "Jigsaw" is being operated
on and begins to convulse: the character performing the surgery yells many times for Ativan, but discovers that
none is available in the limited operating area.

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Blue October mentions Lorazepam in their song "HRSA", where it is being prescribed in a psychiatric ward for a
similar use.

The dependency problem is portrayed in William Gibson's 2007 book Spook Country, in which the character
Milgrim is addicted to Ativan and the character Brown exploits Milgrim's addiction, in order to control him,
through a steady supply of Ativan and Rize (a brand of the benzodiazepine clotiazepam).

In Martin Scorsese's recent film, The Departed, Billy Costigan--an edgy, bitter, intelligent undercover cop for
the Massachusetts State Police--suffers from frequent anxiety, claims to have panic attacks, and is prescribed
lorazepam by a psychiatrist who counsels both police officers and felons.

Blair Waldorf, of the CW's TV show Gossip Girl, mentioned Lorazepam and some other drugs in the fifth
episode of the first season.

In 2005, Fall Out Boy member Pete Wentz attempted suicide by overdosing on lorazepam; he included
references to the episode in the songs "I've Got a Dark Alley and a Bad Idea That Says You Should Shut Your
Mouth (Summer Song)" and "7 Minutes in Heaven (Atavan Halen)",[71] on the album From Under the Cork
Tree.

In Season 6, Episode 2 of The Sopranos, Tony Soprano is also given Ativan for the seizure when he first awakes
from his coma, and is subsequently kept in an induced coma using Ativan.

In the 2009 Broadway musical, Next to Normal, The song, "My Psychopharmacologist and I" contains the
lyrics: "Ativan calms me when I see the bills/These are a few of my favourite pills". Ativan was one of the drugs
found in the cabinet in the movie "The Glass House." Dr. Glass was abusing the medication.

In 2009, Lorazepam was said to have been adminstered to pop music icon Michael Jackson on the morning of
his death by Dr. Conrad Murray as a part of a cocktail of drugs which included Valium and was said to help him
wean off of his use of Propofol. Mr. Jackson's death was attributed to an overdose of the drug Propofol[72] and
Lorazepam.[73]

Also seen in the hit show (season 2 episode 3 red bage) The Mentalist when Agent Lisbon is acussed of murder
it turns out to be her phycologist who druged her with Lorazepam so she would forget parts of the day.

Benzodiazepine
Benzodiazepine dependence
Benzodiazepine withdrawal syndrome
Long term effects of benzodiazepines

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rxlist.com - Lorazepam data sheet (http://www.rxlist.com/cgi/generic/loraz.htm)
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Retrieved from "http://en.wikipedia.org/wiki/Lorazepam"
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