CURRENT DRUG THERAPY
Readers will prescribe antidepressant drugs more confidently on the basis
of the characteristics of the patient and the various drugs
ELIZABETH SHULTZ, DO
DONALD A. MALONE, JR., MD
Department of Psychiatry and Psychology,
Chair, Department of Psychiatry and Psychology,
Cleveland Clinic; Clinical Instructor, Cleveland Cleveland Clinic; Professor, Cleveland Clinic Lerner
Clinic Lerner College of Medicine of Case
College of Medicine of Case Western Reserve
Western Reserve University, Cleveland, OH
University, Cleveland, OH
A practical approach to prescribing
ith the variety of drugs available for
treating depression, choosing one can be
Although antidepressant drugs do not differ much in their daunting. Different agents have characteristics
efficacy rates, the particular characteristics of one drug
that may make them a better choice for dif-
may make it a better choice in a given patient. This article ferent types of patients, but even so, treating
provides insight into the art of prescribing antidepres-
any kind of mental illness often requires an el-
sants in primary care, with recommendations for prescrib-
ement of trial and error.
ing for patients with chronic pain, sexual dysfunction,
Primary care providers are on the frontline
of treating mental illness, often evaluating pa-
anxiety, chronic fatigue syndrome, fibromyalgia, severe
tients before they are seen by a psychiatrist.
insomnia, old age, diabetes, and heart problems.
The purpose of this article is to provide insight
into the art of prescribing antidepressants in the
primary care setting. We will discuss common
We suggest that clinicians become familiar with one drug patient presentations, including depressed pa-
from each class of antidepressants.
tients without other medical comorbidities as
well as those with common comorbidities, with
our recommendations for first-line treatment.
Many antidepressants are also approved for conditions
We hope our recommendations will help
other than depression, and for patients who have both
you to navigate the uncertainty more confi-
depression and one or more of these comcomitant condi-
dently, resulting in more efficient and tailored
tions, these drugs can have a "two-for-one" benefit.
treatment for your patients.
Adverse effects of an antidepressant are usually predict-
■ BASELINE TESTING
able on the basis of the drug's mechanism of action.
When starting a patient on antidepressant
drug therapy, we recommend obtaining a set
of baseline laboratory tests to rule out underly-
ing medical conditions that may be contrib-
uting to the patient's depression or that may
preclude the use of a given drug. (For example,
elevation of liver enzymes may preclude the
use of duloxetine.) Tests should include:
• A complete blood cell count
• A complete metabolic panel
• A thyroid-stimulating hormone level.
Electrocardiography may also be useful, as
some antidepressants can prolong the QT in-
terval or elevate the blood levels of other drugs
with this effect.
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 80 • NUMBER 10 OCTOBER 2013
every 2 weeks based on tolerance and patient
Drugs discussed this article
response. That said, each patient may respond
differently, requiring perhaps a lower starting
Bupropion (Wellbutrin, Zyban)
dose or a longer titration schedule.
Anticipate side effects.
Most of the side ef-
fects of an antidepressant drug can be explained
by its mechanism of action. Although side ef-
fects should certainly be considered when
choosing an agent, patients can be reassured
that most are transient and benign. A detailed
discussion of side effects of antidepressant drugs
is beyond the scope of this article, but a review
by Khawam et al1 was published earlier in this
Maprotiline (Deprilept, Ludiomil, Psymion)
If after 4 to 6 weeks the patient
has had little or no response, it is reasonable
to switch agents. For a patient who was on
Nortriptyline (Aventyl, Pamelor, Norpress)
an SSRI, the change can be to another SSRI
or to an SNRI. However, if two SSRIs have
already failed, then choose an SNRI. Agents
are commonly cross-tapered during the switch
to avoid abrupt cessation of one drug or the
increased risk of adverse events such as cy-
tochrome P450 interactions, serotonin syn-
drome, or hypertensive crisis (when switching
to an MAO inhibitor).
Beware of interactions.
All SSRIs and
SNRIs are metabolized through the P450 sys-
■ GENERAL TREATMENT CONSIDERATIONS
tem in the liver and therefore have the poten-
tial for drug-drug interactions. Care must be
at half the
There are several classes of antidepressants, taken when giving these agents together with
and each class has a number of agents. Re-
drugs whose metabolism can be altered by
search has found little difference in efficacy
P450 inhibition. For TCAs, blood levels can
among agents. So to simplify choosing which
be checked if there is concern about toxicity;
one to use, we recommend becoming comfort-
however, dosing is not strictly based on this
able with an agent from each class, ie:
level. Great care should be taken if a TCA is
• A selective serotonin reuptake inhibitor given together with an SNRI or an SSRI, as
the TCA blood level can become significantly
• A selective serotonin-norepinephrine reup-
elevated. This may result in QT interval pro-
take inhibitor (SNRI)
longation, as mentioned earlier.
• A tricyclic antidepressant (TCA)
Referral to a psychiatrist is appropri-
• A monoamine oxidase (MAO) inhibitor.
ate for patients for whom multiple classes have
Each class includes generic agents, many of
failed, for patients who have another psychiat-
which are on the discount lists of retail phar-
ric comorbidity (such as psychosis, hypomania,
macies. TABLE 1
shows representative drugs from
or mania), or for patients who may need hos-
each class, with their relative costs.
pitalization. Referral is also appropriate if the
Start low and go slow.
In general, when
physician is concerned about suicide risk.
starting an antidepressant, consider starting at
half the normal dose, titrating upward as toler-
■ PATIENTS WITH MAJOR DEPRESSION ONLy
ated about every 14 days. This approach can
minimize side effects. For example, if prescrib-
For a patient presenting with depression but
ing fluoxetine, start with 10 mg and titrate no other significant medical comorbidity, the
626 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 80 • NUMBER 10 OCTOBER 2013
SHULTZ AND MALONE
first-line therapy is often an SSRI. Several ge-
neric SSRIs are available, and some are on the
discount lists at retail pharmacies.
Symptoms should start to improve in about
Class and examples Typical daily dose
Maximum dose Cost a
2 weeks, and the optimal response should be
achieved in 4 to 6 weeks of treatment. If this
Tricyclic antidepressants (TCAs)
does not occur, consider either adding an aug-
25–150 mg, b,c
menting agent or switching to a different anti-
■ PATIENTS WITH CHRONIC PAIN
Chronic pain and depression often go hand
in hand and can potentiate each other. When
Selective serotonin reuptake inhibitors (SSRIs)
considering an antidepressant in a patient who
has both conditions, the SNRIs and TCAs
are typically preferred. Some SNRIs, namely
duloxetine and milnacipran, are approved
for certain chronic pain conditions, such as
fibromyalgia. SNRIs are frequently used off-
label for other chronic pain conditions such as
headache and neuropathic pain.2
TCAs such as amitriptyline, nortriptyline,
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
and doxepin are also often used in patients
with chronic pain. These agents, like the
SNRIs, inhibit the reuptake of serotonin and
norepinephrine and are used off-label for neu-
ropathic pain,3,4 migraine, interstitial cystitis,5
and other pain conditions.6–9
For TCAs and SNRIs, the effective dose
range for chronic pain overlaps that for de-
25–200 mg for sleep b 600 mg
pression. However, TCAs are often given at
150 mg for depression d
lower doses to patients without depression.
We recommend starting at a low dose and
Dopamine-norepenphrine reuptake inhibitor
slowly titrating upward to an effective dose.
SNRIs are often preferred over TCAs because
they do not have anticholinergic side effects
and because an overdose is much less likely to
■ PATIENTS WITH SEXUAL DySFUNCTION
Monoamine oxidase (MAO) inhibitors
One of the more commonly reported side ef-
fects of antidepressants is sexual dysfunction,
generally in the form of delayed orgasm or de-
Tranylcypromine 10–30 mg
creased libido.10 Typically, these complaints
are attributed to SSRIs and SNRIs; however,
a $ = on discount list ($4 or less for 30-day supply), $$ = generic available or relatively
TCAs and MAO inhibitors have also been as-
low-cost brand name, $$$ = no generic available b At bedtime
sociated wth sexual dysfunction.
c Can be divided
Both erectile dysfunction and priapism
d In divided doses
have been linked to certain antidepressants.
e Depending on formulation f Selegiline transdermal system (Emsam patch)
In particular, trazodone is a known cause of
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 80 • NUMBER 10 OCTOBER 2013
priapism. Even if using low doses for sleep, ful for nighttime anxiety, as they can aid sleep.
male patients should be made aware of this Of note, the anxiolytic effect of mirtazapine
may be greater at higher doses.
Switching from one agent to another in MAO inhibitors often go unused because
the same class is not likely to improve sexual
of the dietary and medication restrictions in-
side effects. In particular, all the SSRIs are volved. However, very refractory cases of cer-
similar in their likelihood of causing sexual tain anxiety disorders may respond preferen-
dysfunction. In a patient taking an SSRI who
tially to these agents.
experiences this side effect, switching to bu-
Bupropion tends to be more activating
propion11 or mirtazapine12 can be quite useful.
than other antidepressants, so is often avoided
Bupropion acts primarily on dopamine and in anxious patients. However, some research
norepinephrine, whereas mirtazapine acts on
suggests this is not always necessary.20 If the
serotonin and norepinephrine but in a differ-
anxiety is secondary to depression, it will of-
ent manner from SSRIs and SNRIs.
ten improve significantly with this agent.
Adjunctive treatment such as a choliner-
When starting or increasing the dose of an
gic agonist, yohimbine (contraindicated with
antidepressant, patients may experience in-
MAO inhibitors), a serotonergic agent (eg, creased anxiety or feel "jittery." This feeling
buspirone), or a drug that acts on nitric oxide
usually passes within the first week of treat-
(eg, sildenafil, tadalafil) may have some utility
ment, and it is important to inform patients
but is often ineffective. Dose reduction, if pos-
about this effect. "Start low and go slow" in
sible, can be of value.
patients with significant comorbid anxiety.
Temporarily using a benzodiazepine such as
■ PATIENTS WITH ANXIETy
clonazepam may make the transition more
Many antidepressants are also approved for
anxiety disorders, and still more are used off-
■ PATIENTS WITH CHRONIC FATIGUE
label for this purpose. Anxiety and depression
SyNDROME OR FIBROMyALGIA
often occur together, so being able to treat
both conditions with one drug can be quite
Increasing recognition of both chronic fa-
useful.13 In general, the antidepressant effects
tigue syndrome and fibromyalgia has led to
are seen at lower doses of SSRIs and SNRIs,
more proactive treatment for these disorders.
whereas more of the anxiolytic effects are seen
Depression can go hand in hand with these
at higher doses, particularly for obsessive-
disorders, and certain antidepressants, namely
about 2 weeks
the SNRIs, can be useful in this population.
First-line treatment would be an SSRI or More data exist for the treatment of fibro-
SNRI. Most anxiety disorders respond to ei-
myalgia. Both duloxetine and milnacipran are
ther class, but there are some more-specific approved by the US Food and Drug Adminis-
recommendations. SSRIs are best studied in
tration (FDA) for the treatment of fibromyal-
panic disorder, generalized anxiety disorder, gia.21 Venlafaxine is also used off-label for this
social anxiety disorder, posttraumatic stress purpose. SSRIs such as fluoxetine and citalo-
disorder, and obsessive-compulsive disorder. pram have had mixed results.21–23 TCAs have
Fluoxetine, citalopram, escitalopram, and been used with some success; however, their
sertraline15 can all be effective in both major
side effects and lethal potential are often lim-
depressive disorder and generalized anxiety iting.21,24,25 A recent study in Spain also sug-
disorder. Panic disorder also tends to respond
gested there may be benefit from using MAO
well to SSRIs. SNRIs have been evaluated pri-
inhibitors for fibromyalgia, but data are quite
marily in generalized anxiety disorder but may
also be useful in many of the other conditions.
The data for treating chronic fatigue syn-
Additionally, mirtazapine (used off-label)12
drome with SSRIs, SNRIs, or MAO inhibi-
and the TCAs16–18 can help treat anxiety. Clo-
tors are conflicting.27–29 However, managing
mipramine is used to treat obsessive-compul-
the co-existing depression may provide some
sive disorder.19 These drugs are especially use-
relief in and of itself.
628 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 80 • NUMBER 10 OCTOBER 2013
SHULTZ AND MALONE
■ PATIENTS WITH FREQUENT INSOMNIA
SSRIs, bupropion, and the SNRIs tend not
to affect cognition. Escitalopram and dulox-
Insomnia can be a symptom of depression, but
etine have been suggested to be particularly
it can also be a side effect of certain antide-
effective in the elderly.35,36 A study from the
pressants. The SSRIs and SNRIs can disrupt
Netherlands linked SSRIs with increased risk
sleep patterns in some patients by shortening
of falling in geriatric patients with dementia.37
the rapid-eye-movement (REM) stage.30,31
Constipation, which could lead to ileus, is in-
In patients with severe insomnia, it may be
creased with TCAs and certain other agents
best to first recommend taking the antidepres-
(ie, paroxetine) in the geriatric population.
sant in the morning if they notice worsening
Mirtazapine is often very useful in elderly
sleep after initiating treatment. Patients can
patients for many reasons: it treats both anxi-
be told with any antidepressant, "If it makes
ety and depression, stimulates appetite and
you tired, take it at night, and if it wakes you
weight gain, can help with nausea, and is an
up, take it in the morning." Of note, a recent
effective sleep aid. Concerns about weight,
South African study suggested that escitalo-
appetite, and sleep are particularly common
pram may be able to improve sleep.32
in the elderly, whereas younger patients can
If that does not solve the problem, there are
be less tolerant of drugs that make them gain
other options. For instance, mirtazapine, par-
weight and sleep more. Normal age-related
ticularly in doses of 15 mg or 30 mg, aids depres-
changes to the sleep cycle contribute to de-
sion and insomnia. At higher doses (45 mg), the
creased satisfaction with sleep as we age. In
sleep-aiding effect may be reduced. Low doses
addition, depression often further impairs
of TCAs, particularly doxepin, maprotiline sleep. So, in the elderly, optimizing sleep is
(technically speaking, a tetracyclic antidepres-
key. Research has also shown mirtazapine to
sant), amitriptyline, and nortriptyline can be be effective in patients with both Alzheimer
effective sleep aids. These agents may be used
dementia and depression.38
as an adjunct to another antidepressant to en-
hance sleep and mood. However, the TCAs also
■ DIABETIC PATIENTS
shorten the REM stage of sleep.33
The previously mentioned drug interac-
One of the more worrisome side effects of psy- and depression
tions with SSRIs and SNRIs also need to be
chiatric medications in diabetic patients is
considered. Caution should be used when dis-
weight gain. Certain antidepressants have a often go
continuing these medications, as patients may
greater propensity for weight gain and should hand in hand
experience rebound symptoms in the form of
likely be avoided as first-line treatments in and can
much more vivid dreams. MAO inhibitors this population.12 Typically, these agents in-
may worsen insomnia because they suppress clude those that have more antihistamine ac- potentiate
tion such as paroxetine and the TCAs. These each other
Trazodone is another agent that at lower dos-
agents also may lead to constipation, which
es (25–150 mg) can be an effective, nonaddict-
could potentially worsen gastroparesis. Mir-
ing sleep aid. When used as an antidepressant, it
tazapine and the MAO inhibitors are also
is generally prescribed at higher doses (300–400
known to cause weight gain.
mg), but its sedating effects can be quite limiting
Bupropion and nefazodone are the most
at these levels. It is important to remember the
weight-neutral of all antidepressants. Nefazo-
possibility of priapism in male patients.
done has fallen out of favor because of its po-
tential to cause fulminant liver failure in rare
■ GERIATRIC PATIENTS
cases. However, it remains a reasonable op-
tion for patients with comorbid anxiety and
Old age brings its own set of concerns when
depression who have significant weight gain
treating depression. Elderly patients are more
with other agents.
susceptible to potential bradycardia caused by
SSRIs and MAO inhibitors may improve
SSRIs. The TCAs have the more worrisome
or be neutral toward glucose metabolism, and
cardiac side effect of QTc prolongation. TCAs
some data suggest that SNRIs may impair this
can slow cognitive function, whereas the process.39
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 80 • NUMBER 10 OCTOBER 2013
■ PATIENTS WITH CARDIAC CONDITIONS
lopram at doses greater than 40 mg in adult
patients43; however, research has suggested
Major depression often coexists with cardiac citalopram is effective in treating depression
conditions. In particular, many patients develop
in cardiac patients.44 Research has not shown
depression after suffering a myocardial infarc-
an increase in efficacy at doses greater than
tion, and increasingly they are being treated for
40 mg daily, so we recommend following the
it.40 Treatment in this situation is appropriate,
since depression, if untreated, can increase the
TCAs and MAO inhibitors can also cause
risk of recurrence of myocardial infarction.41
orthostatic hypotension. On the other hand,
However, there are many concerns that consuming large amounts of tyramine, in
accompany treating depression in cardiac foods such as aged cheese, can precipitate a
patients. Therefore, a baseline electrocardio-
hypertensive crisis in patients taking MAO
gram should be obtained before starting an inhibitors.
Which antidepressants tend to be safer in
TCAs and tetracyclic agents have a ten-
cardiac patients? Sertraline has been shown to
dency to prolong the QTc interval and po-
be safe in congestive heart failure and coro-
tentiate ventricular arrhythmias,42 so it may nary artery disease,45–47 but the SSRIs are typi-
be prudent to avoid these in patients at risk.
cally safe. Fluoxetine has shown efficacy in
These agents can also significantly increase patients who have had a myocardial infarc-
the pulse rate. This tachycardia increases the
tion.48 Mirtazapine has also been shown to be
risk of angina or myocardial infarction from
efficacious in cardiac patients.49 Nefazodone,
the anticholinergic effects of these drugs.
mirtazapine, bupropion, SSRIs, and SNRIs
In February 2013, the FDA issued a warn-
have little or no tendency toward orthostatic
ing about possible arrhythmias with cita-
12. Watanabe N, Omori IM, Nakagawa A, et al
. Mirtazapine versus
other antidepressive agents for depression. Cochrane Database Syst
1. Khawam EA, Laurencic G, Malone DA Jr
. Side effects of antidepres-
Rev 2011; 12:CD006528.
sants: an overview. Cleve Clin J Med 2006; 73:351–361.
13. Hofmeijer-Sevink MK, Batelaan NM, van Megen HJ, et al
2. Ziegler D
. Painful diabetic neuropathy: treatment and future as-
relevance of comorbidity in anxiety disorders: a report from the
pects. Diabetes Metab Res Rev 2008; 24(suppl 1):S52–S57.
Netherlands Study of Depression and Anxiety (NESDA). J Affect
3. Saarto T, Wiffen PJ
. Antidepressants for neuropathic pain: a Co-
Disord 2012; 137:106–112.
chrane review. J Neurol Neurosurg Psychiatry 2010; 81:1372–1373.
14. Koen N, Stein DJ
. Pharmacotherapy of anxiety disorders: a critical
4. Tanenberg RJ, Irving GA, Risser RC, et al
. Duloxetine, pregabalin,
review. Dialogues Clin Neurosci 2011; 13:423–437.
and duloxetine plus gabapentin for diabetic peripheral neuropathic
15. Sheehan DV, Kamijima K
. An evidence-based review of the clinical
pain management in patients with inadequate pain response to
use of sertraline in mood and anxiety disorders. Int Clin Psychophar-
gabapentin: an open-label, randomized, noninferiority comparison. Mayo Clin Proc 2011; 86:615–626.
macol 2009; 24:43–60.
5. Hertle L, van Ophoven A
. Long-term results of amitriptyline treat-
16. Huh J, Goebert D, Takeshita J, Lu BY, Kang M
. Treatment of general-
ment for interstitial cystitis. Aktuelle Urol 2010; 41(suppl 1):S61–S65.
ized anxiety disorder: a comprehensive review of the literature for
6. Nguyen TM, Eslick GD
. Systematic review: the treatment of noncar-
psychopharmacologic alternatives to newer antidepressants and
diac chest pain with antidepressants. Aliment Pharmacol Ther 2012;
benzodiazepines. Prim Care Companion CNS Disord 2011; 13: doi:
7. Lee H, Kim JH, Min BH, et al
. Efficacy of venlafaxine for symptom-
17. Rickels K, Downing R, Schweizer E, Hassman H
. Antidepressants for
atic relief in young adult patients with functional chest pain: a
the treatment of generalized anxiety disorder. A placebo-controlled
randomized, double-blind, placebo-controlled, crossover trial. Am J
comparison of imipramine, trazodone, and diazepam. Arch Gen
Gastroenterol 2010; 105:1504–1512.
Psychiatry 1993; 50:884–895.
8. Varia I, Logue E, O'Connor C, et al
. Randomized trial of sertraline
18. Uher R, Maier W, Hauser J, et al
. Differential efficacy of escitalo-
in patients with unexplained chest pain of noncardiac origin. Am
pram and nortriptyline on dimensional measures of depression. Br J
Heart J 2000; 140:367–372.
Psychiatry 2009; 194:252–259.
9. Doraiswamy PM, Varia I, Hellegers C, et al
. A randomized controlled
19. Kellner M
. Drug treatment of obsessive-compulsive disorder. Dia-
trial of paroxetine for noncardiac chest pain. Psychopharmacol Bull
logues Clin Neurosci 2010; 12:187–197.
20. Rush AJ, Trivedi MH, Carmody TJ, et al
. Response in relation to
10. Clayton AH
. Understanding antidepressant mechanism of action
baseline anxiety levels in major depressive disorder treated with
and its effect on efficacy and safety. J Clin Psychiatry 2012; 73:e11.
bupropion sustained release or sertraline. Neuropsychopharmacol-
11. Gartlehner G, Hansen RA, Morgan LC, et al
. Second-generation an-
ogy 2001; 25:131–138.
tidepressants in the pharmacologic treatment of adult depression:
21. Mease PJ, Dundon K, Sarzi-Puttini P
. Pharmacotherapy of fibromyal-
an update of the 2007 comparative effectiveness review (Internet).
gia. Best Pract Res Clin Rheumatol 2011; 25:285–297.
Rockville (MD): Agency for Healthcare Research and Quality (US);
22. Wolfe F, Cathey MA, Hawley DJ
. A double-blind placebo con-
2011 Dec. Comparative Effectiveness Reviews, No. 46. http://www.
trolled trial of fluoxetine in fibromyalgia. Scand J Rheumatol 1994;
ncbi.nlm.nih.gov/books/NBK83442/. Accessed February 27, 2013.
630 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 80 • NUMBER 10 OCTOBER 2013
SHULTZ AND MALONE
23. Arnold LM, Hess EV, Hudson JI, Welge JA, Berno SE, Keck PE Jr
randomized, placebo-controlled, double-blind, flexible-dose study
39. Hennings JM, Schaaf L, Fulda S
. Glucose metabolism and antide-
of fluoxetine in the treatment of women with fibromyalgia. Am J
pressant medication. Curr Pharm Des 2012; 18:5900–5919.
Med 2002; 112:191–197.
40. Czarny MJ, Arthurs E, Coffie DF, et al
. Prevalence of antidepressant
24. Arnold LM, Keck PE Jr, Welge JA
. Antidepressant treatment of
prescription or use in patients with acute coronary syndrome: a
fibromyalgia. A meta-analysis and review. Psychosomatics 2000;
systematic review. PLoS One 2011; 6:e27671.
41. Zuidersma M, Ormel J, Conradi HJ, de Jonge P
. An increase in de-
25. Goldenberg DL, Burckhardt C, Crofford L
. Management of fibromy-
pressive symptoms after myocardial infarction predicts new cardiac
algia syndrome. JAMA 2004; 292:2388–2395.
events irrespective of depressive symptoms before myocardial
26. Tort S, Urrútia G, Nishishinya MB, Walitt B
. Monoamine oxidase
infarction. Psychol Med 2012; 42:683–693.
inhibitors (MAOIs) for fibromyalgia syndrome. Cochrane Database
42. van Noord C, Straus SM, Sturkenboom MC, et al
. Psychotropic drugs
Syst Rev 2012; 4:CD009807.
associated with corrected QT interval prolongation. J Clin Psycho-
27. Vercoulen JH, Swanink CM, Zitman FG, et al
. Randomised, double-
pharmacol 2009; 29:9–15.
blind, placebo-controlled study of fluoxetine in chronic fatigue
43. US Food and Drug Administration (FDA)
. FDA Drug Safety Com-
syndrome. Lancet 1996; 347:858–861.
munication: abnormal heart rhythms associated with high doses of
28. Natelson BH, Cheu J, Pareja J, Ellis SP, Policastro T, Findley TW
Celexa (citalopram hydrobromide). http://www.fda.gov/Drugs/
Randomized, double blind, controlled placebo-phase in trial of low
DrugSafety/ucm269086.htm. Accessed August 25, 2013.
dose phenelzine in the chronic fatigue syndrome. Psychopharmacol-
44. Lespérance F, Frasure-Smith N, Koszycki D, et al; CREATE Investi-
ogy (Berl) 1996; 124:226–230.
. Effects of citalopram and interpersonal psychotherapy on
29. Reid S, Chalder T, Cleare A, Hotopf M, Wessely S
. Chronic fatigue
syndrome. BMJ 2000; 320:292–296.
depression in patients with coronary artery disease: the Canadian
30. Kupfer DJ, Spiker DG, Coble PA, Neil JF, Ulrich R, Shaw DH
Cardiac Randomized Evaluation of Antidepressant and Psychothera-
and treatment prediction in endogenous depression. Am J Psychia-
py Efficacy (CREATE) trial. JAMA 2007; 297:367–379.
try 1981; 138:429–434.
45. O'Connor CM, Jiang W, Kuchibhatla M, et al; SADHART-CHF Inves-
31. Argyropoulos SV, Hicks JA, Nash JR, et al
. Redistribution of slow
. Safety and efficacy of sertraline for depression in patients
wave activity of sleep during pharmacological treatment of depres-
with heart failure: results of the SADHART-CHF (Sertraline Against
sion with paroxetine but not with nefazodone. J Sleep Res 2009;
Depression and Heart Disease in Chronic Heart Failure) trial. J Am
Coll Cardiol 2010; 56:692–699.
32. Stein DJ, Lopez AG
. Effects of escitalopram on sleep problems in
46. Glassman AH, O'Connor CM, Califf RM, et al; Sertraline Antidepres-
patients with major depression or generalized anxiety disorder. Adv
sant Heart Attack Randomized Trial (SADHEART) Group
Ther 2011; 28:1021–1037.
treatment of major depression in patients with acute MI or unstable
33. Ehlers CL, Havstad JW, Kupfer DJ
. Estimation of the time course of
angina. JAMA 2002; 288:701–709.
slow-wave sleep over the night in depressed patients: effects of clo-
47. Swenson JR, O'Connor CM, Barton D, et al; Sertraline Antidepres-
mipramine and clinical response. Biol Psychiatry 1996; 39:171–181.
sant Heart Attack Randomized Trial (SADHART) Group
34. Landolt HP, Raimo EB, Schnierow BJ, Kelsoe JR, Rapaport MH, Gillin
of depression and effect of treatment with sertraline on quality of
. Sleep and sleep electroencephalogram in depressed patients
life after hospitalization for acute coronary syndrome. Am J Cardiol
treated with phenelzine. Arch Gen Psychiatry 2001; 58:268–276.
35. Chen YM, Huang XM, Thompson R, Zhao YB
. Clinical features and
48. Strik JJ, Honig A, Lousberg R, et al
. Efficacy and safety of fluoxetine
efficacy of escitalopram treatment for geriatric depression. J Int
in the treatment of patients with major depression after first myo-
Med Res 2011; 39:1946–1953.
cardial infarction: findings from a double-blind, placebo-controlled
36. Dolder C, Nelson M, Stump A
. Pharmacological and clinical profile
trial. Psychosom Med 2000; 62:783–789.
of newer antidepressants: implications for the treatment of elderly
49. Honig A, Kuyper AM, Schene AH, et al; MIND-IT investigators
patients. Drugs Aging 2010; 27:625–640.
Treatment of post-myocardial infarction depressive disorder: a ran-
37. Sterke CS, Ziere G, van Beeck EF, Looman CW, van der Cammen TJ
domized, placebo-controlled trial with mirtazapine. Psychosom Med
Dose-response relationship between selective serotonin re-uptake
inhibitors and injurious falls: a study in nursing home residents with dementia. Br J Clin Pharmacol 2012; 73:812–820.
ADDRESS: Donald A. Malone, Jr., MD, Department of Psychiatry and Psy-
38. Raji MA, Brady SR
. Mirtazapine for treatment of depression and
chology, P57, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195;
comorbidities in Alzheimer disease. Ann Pharmacother 2001;
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Necrotic Enteritis: Managing without Antibiotics Dr. Linnea J. Newman Schering-Plough Animal Health (presented at the PIC's Poultry Health Conference on November 14, 2000) The medical community has expressed concern that antibiotic use in food animals may promote the development ofantibiotic-resistant strains of bacteria that could threaten the human population. While the true relationship betweenantibiotic use in animals and antibiotic-resistant bacteria in humans has yet to be determined, there has been a strong outcryfrom consumers to eliminate antibiotic use from food animal production.
Compilation and Review of Published and Unpublished Tea Tree Oil Literature A report for the Rural Industries Research and Development Corporation by CF Carson, KA Hammer, TV Riley RIRDC Publication No 05/151 RIRDC Project No UWA-75A © 2005 Rural Industries Research and Development Corporation. All rights reserved. ISBN 1 74151 214 X ISSN 1440-6845 Compilation and Review of Published and Unpublished Tea Tree Oil Literature Publication No. 05/151 Project No. UWA-75A The views expressed and the conclusions reached in this publication are those of the author and not necessarily those of persons consulted. RIRDC shall not be responsible in any way whatsoever to any person who relies in whole or in part on the contents of this report. This publication is copyright. However, RIRDC encourages wide dissemination of its research, providing the Corporation is clearly acknowledged. For any other enquiries concerning reproduction, contact the Publications Manager on phone 02 6272 3186. Researcher Contact Details