Review Articles

Nonenteral Routes of Administration for

Psychiatric Medications
A Literature Review
DIANE THOMPSON, M.D.
ANDREA DIMARTINI, M.D.

In the treatment of psychiatric patients with complicating medical illness, clinicians may encounter patients who cannot take oral medications. This review will acquaint the practicing clinical
psychiatrist with psychotropic medications available by nonenteral routes of administration. A
computerized MEDLINE search was conducted of the literature 1981 to 1997. All articles citing
nonenteral routes of psychotropic medication administration were reviewed. The results are summarized according to drug class and specific routes of administration (intravenous, intramuscular, sublingual, rectal). Psychotropic medications now available by these alternative routes are
also listed in table form. The majority of the information available comes from small case series
or case reports. Intravenous and intramuscular routes of administration of psychotropics are the
most common. In addition, certain psychotropics are available by less common routes, such as
sublingual or rectal administration. Consideration of alterations in pharmacokinetics, including
poorer absorption and slower metabolism, are discussed. Clinicians may need to consider these
novel routes of medication administration when dealing with patients unable to take oral medications.
(Psychosomatics 1999; 40:185192)

dministering psychiatric medications to patients unable to tolerate oral dosing or physiologically incapable of intestinal absorption creates a clinical dilemma for
physicians treating such medically complicated patients. In
the medical population, the prevalence of psychiatric illness can be great. For example, 30% to 50% of patients
diagnosed with cancer meet criteria for a psychiatric illness.1 Nausea, emesis, nothing-by-mouth restrictions, or
anatomical deficits, such as gastric or bowel dysfunction
or resection, can prevent or delay treatment with oral medications. In these situations, withholding or delaying treatment with psychiatric medications and can cause significant distress to patients with a mental disorder and may
not be necessary.
Currently, there is little published information and few
clinical guidelines for alternative routes of administration
Psychosomatics 40:3, May-June 1999

for psychiatric medications. In addition to injectable psychotropic medications (see Santos et al.2 for a comprehensive review),we will focus on other less common routes of
administration. This review will cover the availability of
intravenous, intramuscular, sublingual, and rectal administration of antipsychotics, antidepressants, stimulants,
mood stabilizers, and anxiolytics.
Most psychotropic medications are not specifically
made for other than oral administration. Therefore, using
such medications by alternative routes may significantly
alter the expected pharmacokinetics of the oral preparation
and may necessitate a pharmacologic alteration in the medReceived July 17, 1998; accepted August 19, 1998. From the Magee
Womens Hospital, 300 Halket Street, Pittsburgh, PA 15213. Address correspondence and reprint requests to Dr. Thompson at the same address.
Copyright q 1999 The Academy of Psychosomatic Medicine.

185

Routes of Administration
ication or vehicle of administration. For example, medications need to be in solution to passively diffuse through
membranes. Many psychotropics (e.g., phenothiazines, tricyclic antidepressants, and many benzodiazepines) are
weak bases and are best dissolved in the acidic stomach,
where they are in an ionized form.3 Optimal absorption via
passive diffusion occurs in the alkaline environment of the
small intestine.4 If such a drug is administered sublingually
or rectally, the required mucosal environment and pH (hydrogen ion concentration) in that area of the gastrointestinal tract may not be sufficient for dissolution or diffusion.
Once absorbed, depending on the location of the vasculature and the site of administration, bypassing the effect of
first-pass metabolism can cause a significant increase in
bioavailability, compared with oral administration.57 The
administration of medications via alternative routes must,
therefore, be adjusted accordingly, as the bioavailability is
increased or decreased.
SPECIFIC ROUTES OF ADMINISTRATION
Intravenous
Intravenous psychotropic medications have been
widely used for decades for general anesthesia, sedating agitated patients, and relieving symptoms of anxiety. However,
other than some phenothiazines, butyrophenones, and some
benzodiazepines, most psychotropic medications, particularly the newer antidepressants, do not come in intravenous
forms. In addition, though intravenous administration of an
antipsychotic is a frequent clinical practice, it is not Federal
Drug Administration-approved for psychiatric disorders.8
Good distribution by avoidance of first-pass metabolism are
key factors in this route of administration. Difficulties occur
with complications such as infiltration, risk of infection, and
difficulty with venous access.
Intramuscular
This method is often used for rapid tranquilization in
an emergency setting because of fast absorption and increased bioavailability.9 Depot antipsychotics are also administered intramuscularly. Their rate-limiting step is the
release of the medication from the depot solution, which
is dependent on the amount of subcutaneous fat. In addition, first-pass metabolism is avoided.5 In patients with reduced muscle perfusion, such as in cardiac insufficiency,
intramuscular injections should be avoided. Daily injections of tricyclics or antipsychotics may be undesirable to
186

the patient and may also lead to muscle irritation, necrosis,

or abscesses.
Sublingual/Buccal
The abundance of sublingual capillaries, their proximity to the mucosal layer, and the efficacy of sublingual
medications such as nitroglycerin suggest this route as a
possible option for psychotropic medication administration. Although minimal research has been done, this may
be an effective route, especially for nonionized, highly
lipid-soluble medications. Pharmacokinetic models show
that increasing the concentration of the nonionized, lipidsoluble form of the drug increases the percentage of buccal
drug absorption.10 Haloperidol, chlorpromazine, clomipramine, diazepam, nitrazepam, promethazine, and trihexyphenidyl are examples of nonionized, highly lipophilic
drugs11 that may diffuse across the mucosal membranes at
physiologic pH (pH 7.4). Venous drainage via the oral mucosa is superior to the vena cava and avoids first-pass hepatic metabolism completely.12 Patients with severe nausea, such that any oral stimulation is intolerable, may not
benefit from this form. In addition, many medications may
have a bitter taste, creating further nausea.
Rectal
Patients who will not tolerate any gastric stimulation
may benefit from a medication that can be absorbed rectally. This may be particularly useful for patients who cannot tolerate sublingual medication and for those who are
not likely to tolerate daily intramuscular or intravenous
dosing. The absorption is expected to be somewhat incomplete with rectal administration. The drug preparation and
vehicle are important with hydrophilic solutions, resulting
in improved absorption.13 Larger volumes increase the bioavailability by increasing the mucosal surface in contact
with the drug,13 though a larger volume enema may be
uncomfortable for the patient. As with buccal absorption,
only the nonionized moiety of a drug will be available for
transmucosal diffusion, and this will be affected by the pH
of the rectum.13 For enema administration, the pH of the
solution can be increased to improve absorption, as long
as the rectal mucosa is not irritated. A substantial portion
of the venous drainage from the perivascular rectal plexus
travels through the rectal veins to the iliac veins and ultimately enters the inferior vena cava, thereby avoiding the
portal vein and first-pass hepatic metabolism. Fifty percent
of a rectally absorbed medication will bypass first-pass mePsychosomatics 40:3, May-June 1999

Thompson and DiMartini

tabolism in the liver.3 Patients may prefer suppository
forms of medication to enemas.
PSYCHOTROPIC MEDICATIONS
There is limited clinical experience on the administration
of psychotropic medications by nonenteral routes, and the
information available comes from case reports and small
clinical trials. Most of these medications are available in
the United States, although not necessarily approved for
psychiatric administration by alternative routes. Medications available in other forms in other parts of the world
are also briefly discussed. In some cases, psychotropic
medications were specially compounded by pharmacists to
allow administration by a novel alternative route.
Antipsychotics
Though several antipsychotic medications are listed as
having intravenous preparations, only intravenous haloperidol is described in the literature for use in the treatment
of psychosis and agitation.1416 In the case of haloperidol,
pharmacokinetics play a significant role40% less is
available via the oral route, compared with intravenous administration.17 Cardiovascular or neurologic complications
from intravenous haloperidol were not noted in one study
of patients with cardiac disease,14 though QT interval prolongation and Torsades de Pointes arrhythmia were described in three patients receiving intravenous haloperidol.18 These three patients had cardiac disease, dilated
cardiomyopathy, and histories of longstanding alcohol
abuse. The authors recommended the use of intravenous
haloperidol be accompanied by cardiac monitoring (at least
baseline electrocardiogram (ECG), measurement of QT
and QTc intervals, and ECG reassessment on haloperidol)
and the assessment for risk factors such as alcohol abuse
or cardiac disease.15 Extrapyramidal side effects occur less
frequently with intravenous administration.14,19 Droperidol
is also available in intravenous form and is more sedating
than haloperidol. However, because droperidol is rapidly
absorbed from the site of injection, the response to intramuscular is difficult to distinguish from intravenous administration.8 The risk of hypotension (due to greater peripheral alpha-adrenergic blockage) may limit the use of
droperidol in the medically compromised.
Antidepressants
While the tricyclic antidepressant clomipramine is
available in intravenous form in Europe, it and all other
Psychosomatics 40:3, May-June 1999

antidepressants are not widely available in forms other than

oral in the United States. There are few case reports of
rectal administration and no reports of sublingual use. Intramuscular and intravenous administrations have been
used but are not currently available in the United States.
Of additional interest, animal studies have shown that
down-regulation of beta-adrenergic receptors, which may
be involved in therapeutic response, can rapidly be
achieved by intravenous infusion.20,21
The use of amitriptyline and cocoa butter in a 50milligram suppository was reported to improve mood and
sleep in a woman with colonic adenocarcinoma.22 Amytriptyline serum levels were not measured. A second report of
tricyclic suppositories consisted of four patients who received
doxepin capsules with no suppository base in 25-milligram
form. The patients received up to 50 milligrams, and three
of the four had therapeutic levels after 2 to 5 days at their
maximum dose.23 The authors noted improvement in neuropathic pain but did not assess depressive symptoms.
Intravenous clomipramine has been used in several
studies, including a randomized trial of oral vs. pulseloading intravenous clomipramine.24 Twenty-two hospitalized patients with a major depressive disorder were given
either a 150-milligram dose of clomipramine hydrochloride intravenously or a 150-milligram oral dose. An increased dose of 200 mg was repeated 24 hours later. Five
days later, a significant improvement was noted in both
groups on the Hamilton Depression Rating Scale, the Raskin Severity for Depression Scale, and the Beck Depression
Inventory.
Intramuscularly administered imipramine was compared with the oral form in 18 depressed hospitalized patients.25 Two mg/kg/day were administered intramuscularly for 14 days. On Day 14, the mean plasma
concentrations for imipramine were between 8258.5 ng/
ml to 112.2 58.0 ng/ml. Oral imipramine was then administered from Day 15 to Day 21. The daily dose had to
be doubled to maintain the plasma levels reached with the
intramuscular dose.
We recently administered fluoxetine enemas to a patient
with major depression who has no stomach or small intestine
(unpublished data). Fluoxetine (20 mg in 30 cc of sterile water) was administered rectally once in the morning. Pharmacokinetic studies demonstrated absorption, though serum
levels remained subtherapeutic at 1, 3, 6, 12, and 18 hours
postadministration (fluoxetine range: 3040 ng/mL and norfluoxetine range: 3743 ng/mL during the 18-hour period).
Though she experienced some improvement in mood and
affect, she did not have a complete clinical response. In ad187

Routes of Administration
dition, as the dosage was increased, she was unable to tolerate
the enemas because of abdominal cramping that occurred
shortly after administration and persisted for several hours
after dosing. We believed the cramping was caused by introduction of air into the colon, the isotonic solution, or the
serotonergic features of fluoxetine.
Newer classes of antidepressants, including buproprion, venlafaxine, and mirtazapine, have no data on alternative routes of administration. Similarly, the monoamine
oxidase inhibitors are only available in oral form, and there
are no reports of administering via a different route in U.S.
studies. However, as with several other medications, the
monoamine oxidase inhibitor moclobemide was administered in both the oral and intravenous form in a comparative study in Europe.26 Intravenous citalopram, a selective
serotonin reuptake inhibitor, is available in Europe for use
in treatment-resistant depression. Infusions of 20 mg, increased to 40 mg, are followed in 1014 days, with oral
therapy based on the same dosage.27 Other novel routes of
administration such as topical application are now being
explored, but additional data are not yet available on these
innovative alternatives.
Psychostimulants
Psychostimulants are being used for medically ill patients and have been shown to be an effective treatment for
depression2830 and as an adjuvant to narcotic analgesics.31
The recommended route for stimulant medication is oral,
though two case reports suggest buccal absorption and suppository form may also be effective. Intravenous forms
have also been used for research purposes.
The first study reported describes the use of pemoline
in four patients.32 In two of the cases, the authors describe
the administration via buccal absorption. In the first case,
a woman with intermittent bowel obstruction was given
pemoline in a chewable tablet that could be absorbed from
the buccal mucosa. Her dose was titrated to 37.5 milligrams
bid, and improvement in mood and energy was noted in 4
days. The next case concerned a man with gastric cancer.
He was given a 37.5-milligram tablet of pemoline to suck
on and instructed to dissolve the tablet in his mouth. His
dose was also increased to 37.5 milligrams twice a day,
with improvement in affect and concentration.
Beckett et al. evaluated buccal absorption of stimulants at varying pH.33 Male subjects were given a 25milliliter solution of amphetamine, methylamphetamine, or
dimethylamphetamine. They were instructed to hold the
solution in their mouths for 5 minutes without swallowing
188

and to circulate it about once/second (perhaps to increase

contact with the mucosa). The researchers found superior
absorption of these drugs at a high pH (9.18), with a range
of 68.5 % to 88.5% absorption.
Another report describes the use of dextroamphetamine
suppositories in a woman with gastrointestinal obstruction.34
Dextroamphetamine suppositories in 5-milligram form were
devised by the pharmacy and administered in the morning.
Though the milligram dosage used was not specified, the
author notes significant improvement in the patients mood
and affect. Symptoms recurred with discontinuation of the
stimulant and abated once the medication was resumed.
Methylphenidate has been abused intravenously and
can result in pulmonary disorders attributable to pill fragments.35,36 An intravenous form is not commercially available; however, it has been used for research purposes. A
1985 study found no relationship between an initial response to intravenous methylphenidate and response to zimeldine, a relatively serotonergic antidepressant.37 Fifteen
depressed patients received 0.3 milligram of intravenous
methylphenidate per kilogram body weight. They were assessed 50 minutes later by the author and self-reports. Nine
had a positive response, five had a negative response, and
one experienced no change. The self-reports were based on
four scales that assessed happy/sad, lethargic/energetic, unfriendly/friendly, and mind blank/racing. The author also
rated the subjects according to a global change in mood.
No untoward events were noted.
Though not used for psychiatric purposes, intravenous
D-amphetamine was administered with placebo, pimozide,
or lithium to determine effects on norepinephrine, dopaminebeta-hydroxylase, pulse rate, and blood pressure in schizophrenic patients.38 Twenty milligrams of D-amphetamine
were given intravenously. Norepinephrine increased by
188556 pg/ml; however, the dopamine-beta-hydroxylase
did not change significantly. Pulse rates with D-amphetamine
increased by a mean of 11520 beats per minute, and both
systolic and diastolic blood pressure were significantly increased. The mean systolic change was 26525 torr, and the
mean diastolic change was 10512 torr. While there were no
medical complications recorded, it is important to note that
neither of these studies included medically compromised patients, who may not tolerate the cardiovascular changes.
Mood Stabilizers
Lithium, valproate, and carbamazepine are the current
medications available in nonoral forms for stabilization of
mood. Lithium is only available in oral form in the United
Psychosomatics 40:3, May-June 1999

Thompson and DiMartini

States. Lithium oligosol is a sublingual medication that
achieves detectable plasma levels in patients in Europe.39
Studies with intravenous lithium and intraperitoneal lithium offer other possibilities. A case report demonstrates
that intraperitoneal lithium can be administered to bipolar
patients with end-stage renal disease.40 In this report, lithium was first used intramuscularly, but there are no details
of administration. The procedure for the intraperitoneal
lithium solution consisted of dissolving 89 milligrams of
lithium chloride in 5 milliliters of sterile water, which was
filtered and collected so that each milliliter contained 17.8
milligrams of lithium chloride. Eighty and one-tenth milligrams were added to every two-liter bag of dialysate.
There was an improvement in mania with the treatment,
and serum lithium correlated well with dialysate lithium.
Lithium clearance of 10 to 15 milliliters per minute approximates normal renal function.
Another 1987 study used intravenous lithium to determine its effect on cerebral electrical activity.41 A 41year-old, bipolar patient received lithium 15 milliliters
twice a day for 10 days. On Day 10, the plasma concentration was 0.85 mm/L, and the erythrocyte concentration
was 0.13 mm/L. The authors note no clinical neurotoxicity,
but a slowing of electroencephalogram activity was observed with the lithium monotherapy.
Although there are no known studies on the use of
valproic acid suppositories and retention enemas for mood
stabilization, they have been used for treatment of status
epilepticus.42,43 The serum concentration of valproic acid
in a rectal suppository was compared with the oral dose in
six males.44 The mean absorption was 80%; however, it
took 3.1 hours for the suppository to reach maximum concentration vs. 1 hour for the oral form. The serum concentration of equivalent doses (500 milligrams) was 43.4 milligrams per liter in the oral dose and 29.2 milligrams per
liter for the suppository.
A similar study was done with rectally administered
carbamazepine vs. oral administration in healthy subjects.45 While rectal absorption was slower, the bioavailability was similar. The authors concluded that the suppository can be given in doses equivalent to the oral form.
Another report describes the use of carbamazepine, doxepin, or both in six cancer patients with severe pain or seizures. The carbamazepine was crushed, placed in gelatin
capsules, and inserted into the rectum. At doses of 600
milligrams bid or tid, five of the six patients reached therapeutic levels; all showed clinical improvement.20 There
were no further seizures in the two patients with prior seizures, and the patients were more comfortable.
Psychosomatics 40:3, May-June 1999

Abbott Laboratories now have valproate sodium injection for the treatment of partial and complex seizures.
The intravenous administration was developed for patients
who cannot take the oral form.46 This approach may be a
promising alternative for medically ill patients who were
taking valproate sodium for mood stabilization, and now
are not able to take oral medications.
Anxiolytics
While there are no reports of nonenteral routes for
buspirone, there are several benzodiazepines that can be
administered intramuscularly or intravenously. There are a
few reports on the use of sublingual benzodiazepines and
many on rectal administration of benzodiazepines. Nasal
administration of short-acting benzodiazepines (midazolam) are used for preanesthetic or anesthetic medication
and can even be safely used in children.47 This route for
psychiatric purposes is not reported.
A review paper on the rectal administration on diazepam
concludes that this is an excellent alternative for the management of seizures.48 The author reviewed eight papers,
which concluded that rectally administered intravenous diazepam reaches therapeutic levels in 5 to 10 minutes. Therapeutic levels were between 754 ng/mL and 98.5 ng/mL and
were based on seizure control. According to this review, the
recommended administration is undiluted diazepam intravenous solution inserted with a small syringe.
Sublingual administration is reported infrequently, but
three papers on alprazolam and lorazepam indicate that this
is an effective route. The pharmacokinetics of sublingual
lorazepam were compared with intravenous, intramuscular,
and oral lorazepam in 10 subjects.49 For sublingual and oral
administration, patients were asked to fast overnight and
then received two standard 1-milligram tablets that were
held under the tongue for 15 minutes. Blood samples were
drawn at 5 minutes and then at intervals up to 48 hours for
the 10 subjects. The mean peak plasma concentration was
23.3 ng/mL for the sublingual dose vs. 24.9 ng/mL for the
oral dose. Peak concentration occurred at 2.35 hours for
the sublingual and 2.37 hours for the oral dose. The systemic availability was 94.1% sublingual and 99.8% oral.
The authors conclude that sublingual lorazepam, given on
an empty stomach, could be substituted for both oral and
intramuscular lorazepam.
The kinetics of oral and sublingual alprazolam were
studied in 13 fasting volunteers.50 A 1-milligram tablet was
used for both the oral and sublingual administration, and
blood samples were drawn at 5 minutes and then through189

Routes of Administration
out a 48-hour period. The mean peak plasma concentration
for the sublingual dose was 17.3 nanograms per milliliter
and 14.4 nanograms per milliliter for the oral dose. Time
of peak concentration was 1.17 hours sublingually and 1.73
hours orally. As with lorazepam, sublingual alprazolam is
basically equivalent to the oral dose.
A third mention of sublingual lorazepam or alprazolam is from a letter to the editor and describes one authors
experience.51 The author concludes that lorazepam or alprazolam tablets chewed or held under the tongue give patients relief from panic symptoms in as few as 2 minutes.
There is no discussion of sample size or pharmacokinetics.

CONCLUSIONS
Antipsychotics, antidepressants, stimulants, mood stabilizers, and anxiolytics all have some alternative route of administration, though some preparations are not yet available in the United States. Intravenous and intramuscular
routes are more commonly used but must be adjusted for
first-pass metabolism or alterations in muscle perfusion.
TABLE 1.

Psychiatric medication and routes of adminstration

Medication
Antipsychotics
Chlorpromazine
Triflupromazine
Pomazine
Perphenazine
Trifluoperazine
Fluphenazine
Mesoridazine
Chlorprothixene
Thiothixene
Loxapine
Haloperidol
Droperidol
Tricyclics
Amitriptyline
Doxepin
Stimulants
Methylphenidate
Dextromphetamine
Pemoline
Mood Stabilizers
Lithium
Valproic Acid
Carbamazepine
Anxiolytics
Alprazolam
Chlordiazepoxide
Diazepam
Lorazepam

190

Though incomplete ionization and a different mucosal environment are expected to impede the absorption of rectally
or sublingually administered oral medications, the therapeutic levels and clinical response of medications delivered
by these routes suggests that the pH of the environment,
while important, may not be critical. When available, blood
levels should be monitored to determine absorption. Even
when therapeutic levels are not available, we have used
blood levels to determine if absorption has occurred.
With increasing clinical experience, the availability of
newer options is being explored. Nasal administration of midazolam is possible and perhaps could be extended to other
benzodiazepines. Patches used for the administration of narcotic analgesics may also provide a possible route of administration. In some cases, pharmacists have worked with
the treating physician to compound psychotropic medications
for novel alternative routes. For example, topical administration of psychotropics is now being investigated, though
not enough information exists to recommend this route. However, the currently available alternatives, as outlined in Table
1, provide many useful options for the treatment of those
persons who are not able to take oral medication.

Rectal

Intramuscular

Intravenous

X
X
X
X
X
X
X
X
X
X
X
X

Sublingual

Peritoneal

X
X

X
X
X
X

X
X
X

X
X

X
X
X
X

X
X
X

Psychosomatics 40:3, May-June 1999

Thompson and DiMartini

References

1. Grassi L, Rosti G: Psychosocial morbidity and adjustment to illness

among long-term cancer survivors: a six-year follow-up study. Psychosomatics 1996; 37:523532
2. Santos AB, Beliles KE, Arana GW:Parental use of psychotropic
agents, in Medical-Psychiatric Practice, Vol 2, edited by Stoudemire A, Fogel BS. Washington, DC: American Psychiatric Press;
1985, pp. 113137
3. Greenblatt DJ, Hornatz JS, von Multke LL, et al: Pharmacokinetics
and Pharmacodynamics, in PsychopharmacologyThe 4th Generation of Progress, edited by Bloom FE, Kupfer D. New York,
Raven; 1995, pp. 849858
4. Leipzig R: Psychopharmacology in patients with hepatic and gastrointestinal disease. Int J Psychiatry Med 1990; 20:109139
5. Barnes T, Curson D: Long-term depot antipsychotics: a risk-benefit
assessment. Drug Safe 1994; 10:464479
6. Hiemke C: Paroxetin pharmacokinetics and pharmacodynamics.
Forschritte der Neurologie-Psychiatrie 1994; 1(62 suppl):28
7. van Harten J: Overview of the pharmacokinetics of fluvoxamine.
Clin Pharmacokinet 1995; 1:19
8. Mason AS, Granacher RP: Clinical Handbook of Antipsychotic
Drug Therapy. New York, Brunner/Mazel, 1980, p. 55
9. Dubin W: Rapid tranquilization: antipsychotic or benzodiazepines?
J Clin Psychiatry 1988; 49:511
10. Beckett AH, Triggs EJ: Buccal absorption of basic drugs and its
application as an in vivo model of passive drug transfer through
lipid membranes. J Pharm Pharmacol 1967; 19(suppl):31S41S
11. Ishizaki J, Yokogawa K, Nakashima E, et al: Relationships between
the hepatic intrinsic clearance or blood cell-plasma partion coefficient in the rabbit and the lipohilicity of basic drugs. J Pharm Pharmacol 1997; 49:768772
12. Rathbone MJ, Ponchel G, Ghazali FA: Systemic oral mucosal drug
delivery systems, in Oral Mucosal Drug Delivery, edited by Rathbone MJ. New York, Marcel Dekker, 1996, pp. 241285
13. Jantzen JP, Diehl P: Rectal administration of drugs. Fundamentals
and applications in anesthesia. Anaesthesist 1991; 40:251261
14. Lerner Y, Lwow E, Levitin A, et al: Acute high-dose parental haloperidol treatment of psychosis. Am J Psychiatry 1979; 136:1061
1064
15. Settle E, Ayd FJ: Haloperidol: a quarter-century of experience. J
Clin Psychiatry 1993; 44:440448.
16. Moller H, Kissling W, Lang C, et al: Efficacy and side effects of
haloperidol in psychotic patients: oral versus intravenous administration. Am J Psychiatry 1982; 139:15711575
17. Tesar G, Murray GB, Cassem NH: Use of high-dose intravenous
haloperidol in the treatment of agitated cardiac patients. J Clin Psychopharmacol 1985; 5:344347
18. Metzger E, Friedman R: Prolongation of the corrected QT and Torsades de Pointes cardiac arrythmia associated with intravenous
haloperidol in the medically ill. J Clin Psychopharmacol 1993;
13:128132
19. Menza MA, Murray GB, Holmes VF, et al: Decreased extrapyramidal symptoms with intravenous haloperidol. J Clin Psychiatry
1987; 48:278280
20. Sethy VH, Day JS, Cooper MM: Dose-dependent down-regulation
of beta-adrenergic receptors after chronic intravenous infusion of
antidepressants. Prog Neuropsychopharmacol Biol Psychiatry
1988; 12:673682
21. Sethy VH, Day JS, Cooper MM: Rapid changes in central betaadrenergic receptors after chronic intravenous infusion of antidepressants. Research Communications in Chemical Pathology &
Pharmacology 1986; 54:3546

Psychosomatics 40:3, May-June 1999

22. Adams F: Amytriptyline suppositories. N Engl J Med 1982;

306:1996
23. Storey P, Trumble M: Rectal doxepin and carbamazepine therapy
in patients with cancer. N Engl J Med 1992; 327:13181319
24. Pollock B, Perel JM, Nathan RS, et al: Acute antidepressant effect
following pulse loading with intravenous and oral clomipramine.
Arch Gen Psychiatry 1989; 46:2935
25. Rigal J, Albin H, Fanca X, et al: The influence of the route of
administration of imipramine on imipramine and desipramine
blood levels. J Clin Psychopharmacol 1989;9:364367
26. Raaflaub J, Haefelfinger P, Trautmann KH: Single dose pharmacokinetics of the MAO-inhibitor moclobemide in man. Arzneimittel-Forschung 1984; 34:8082
27. Package insert: seropram as infusion. License Holder: Lundbeck
NV. Manufacturer: Lundbeck H, Denmark
28. Masand P, Pickett P, Murray GB: Psychostimulants for secondary
depression in medical illness. Psychosomatics 1991; 32:203208
29. Pickett P, Masand P, Murray GB: Psychostimulant treatment of geriatric depressive disorders secondary to medical illness. J Geriatr
Psychiatry Neurol 1990; 3:146151
30. Woods S, Tesar GE, Murray GB, et al: Psychostimulant treatment
of depressive disorders secondary to medical illness. J Clin Psychiatry 1986; 47:1215
31. Bruera E, Brenneis C, Paterson AH, et al: Use of methylphenidate
as an adjuvant to narcotic analgesics in patients with advanced cancer. J Pain Symptom Manage 1989; 4:36
32. Breitbart W, Mermelstein H: Pemoline: an alternative psychostimulant for the management of depressive disorders in cancer patients.
Psychosomatics 1992; 33:352356
33. Beckett A, Boyes RN, Triggs EJ: Kinetics of buccal absorption of
amphetamine. J Pharm Pharmacol 1968; 20:9297
34. Holmes T: Psychostimulant suppository treatment for depression
in the gravely ill. J Clin Psychiatry 1994; 55:265266
35. Carteer H, Watson W: IV pentazocine/methylphenidate abusethe
clinical toxicity of another Ts and blues combination. J Toxicol
1994; 32:541547
36. Parran T, Jasinski D: Intravenous methlyphenidate abuse. Prototype
for prescription drug abuse. Arch Intern Med 1991;151:781783
37. Joyce P: Mood response to methylphenidate and the dexamethasone suppression test as predictors of treatment response to zimelidine and lithium in major depression. Biol Psychiatry 1985;
20:598604
38. Rosenblatt J, Lake CR, Van Kammen DP, et al: Interactions of
amphetamine, pimozide, and lithium on plasma norepinephrine and
dopamine-beta-hydroxylase in schizophrenic patients. Psychiatry
Res 1979; 1:4552
39. Allain P, Le Bouil A, Turcant A, et al: Pharmacocinetique du lithium administre a doses faibles chez le volontaire sain. Therapie
1994; 49:321324
40. Flynn CT, Chandran PK, Taylor MJ, et al: Intraperitoneal lithium
administration for bipolar affective disorder in a patient on continuous ambulatory peritoneal dialysis. Int J Artif Organs 1987;
10:105107
41. Beaubernard C, Minot R, Macher JP: Lithium: clinical study by
brain electrical activity mapping. A case report. Pharmacopsychiatry 1987; 20:197202
42. Issakainen J, Bourgeois B: Bioavailability of sodium valproate suppositories during repeated administration at steady state in epileptic
children. Eur J Pediatr 1987; 146:404407
43. Holle LM, Gidal BE, Collins DM: Valproate in status epilepticus.
Ann Pharmacother 1995; 29:10421044

191

Routes of Administration
44. Holmes GB, Rosenfeld WE, Graves NM, et al: Absorption of valproic acid suppositories in human volunteers. Arch Neurol 1989;
46:906908
45. Neuvonen P, Tokola O: Bioavailability of rectally administered carbamazepine mixture. Br J Clin Pharmacol 1987; 24:839841
46. Epilepsy Drug. Clinical Psychiatry News, December, 1997, p.
33
47. Audenaert SM, Wagner Y, Montgomery CL, et al: Cardiorespiratory effects of premedication for children. Anesth Analg 1995;
80:506510

192

48. Seigler R: The administration of rectal diazepam for acute management of seizures. J Emerg Med 1990; 8:155159
49. Greenblatt D, Divoll M, Harmatz JS, et al: Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular,
and oral lorazepam. J Pharm Sci 1982; 71:248252
50. Scavone J, Greenblatt DJ, Shader RI: Alprazolam kinetics following sublingual and oral administration. J Clin Psychopharmacol
1987; 7:332334
51. Grove V: Sublingual benzodiazepines can relieve panic rapidly. Tex
Med 1990; 86:10

Psychosomatics 40:3, May-June 1999