Intervention
Pharmacologic Intervention
Overview
Suicide risk of antidepressant medication
Interferon-related depression
Antidepressant medication selection
Selective serotonin reuptake inhibitors
Discontinuation of antidepressants
Side effects
Drug-drug interactions
Atypical antidepressants
Benzodiazepines
Psychostimulants
Monoamine oxidase inhibitors
St. John's wort
Antidepressant effects
Psychotherapy
Overview
Empirical studies of the efficacy of psychotherapy
Whether to initiate therapy for depression depends on the probability
that the patient will recover spontaneously in the next 2 to 4 weeks, the
degree of functional impairment, and the severity and duration of the
depressive symptoms.[1] Studies have shown that treatment of major depression
is optimized by a combination of pharmacotherapy and psychotherapy. Thus, even
if a primary care physician or oncologist undertakes the treatment of
depressive symptoms pharmacologically, a referral for psychotherapy or
supportive counseling should be considered.
Individuals should be referred for a psychiatric consultation for the following
reasons:
- A primary care physician or oncologist does not feel competent treating the
patient for depression because of specific clinical features in the
presentation (i.e., if prominent suicidal tendencies are present).
- The depressive symptoms treated by the primary physician are resistant to
pharmacologic interventions after 2 to 4 weeks of intervention.
- The depressive symptoms are worsening rather than improving.
- Initiating treatment with antidepressant drugs, titrating drug
doses, or continuing treatment is interrupted or made problematic by
adverse effects attributable to the medication.
- The depressive symptoms are interfering with the patient's ability to be
cooperative with medical treatment.[2-4]
Pharmacologic Intervention
Overview
There is a paucity of randomized, placebo-controlled trials assessing the risks and benefits of antidepressants in patients with cancer and depression or depressive symptoms. Furthermore, these studies are limited by methodological challenges and a lack of broad representation of children, adolescents, older adults, and minority groups.[5] In certain cases of depression in patients with cancer, antidepressant therapy
may be indicated. A survey of prescribing patterns in outpatient oncology settings over a 2-year period found that antidepressants were prescribed for about 14% of patients.[6] In a systematic review of newer pharmacotherapies for
depression in adults, the response rate for treatment of depression with
antidepressants was found to be approximately 54%.[7] The efficacy of the
newer pharmacotherapies is similar to that of older antidepressants for general
medical patients, including older adults and those with coexisting medical or
psychiatric illness.[7] The dropout rates due to adverse effects are
approximately 11% for newer antidepressants and 16% for older
antidepressants.[7] Because of the relative paucity of data regarding antidepressant use in
oncology settings, there is considerable variability in practice patterns
related to prescribing antidepressants in cancer patients. Although studies
generally indicate that about 25% of all cancer patients are depressed, one study found that only 16%
of cancer patients were receiving antidepressant medication.[8]
Antidepressant Studies
- In adults, a double-blind
placebo-controlled trial comparing fluoxetine with desipramine in treating
depressive symptoms in 40 women with cancer found both medications to be
effective and well tolerated. There were greater improvements on several
quality-of-life measures in patients who received fluoxetine.[9]
- One study compared paroxetine with amitriptyline in the management of depression in women with breast cancer. Both treatments were equally effective. Paroxetine was associated with significantly fewer anticholinergic adverse effects than amitriptyline.[10]
- In a randomized controlled trial comparing fluoxetine with a placebo, patients receiving fluoxetine were found to have improved quality of life and decreased depressive symptoms.[11] Using a symptom-based approach (similar to the management of other cancer-related symptoms such as pain or nausea), this study assessed for depression by use of a 2-item screening procedure focused on presence of anhedonia (little interest or pleasure in doing things) and depressed or hopeless mood. Most of the sample consisted of patients with mild-to-moderate levels of depressive symptoms regardless of whether they met the diagnostic criteria for depression. Generalization was enhanced by inclusion of a sample of mixed cancer types (e.g., breast, thoracic, genitourinary, gastrointestinal) from a predominantly community cancer care setting, an equal male/female ratio, and a relatively large sample size (n = 163). A subgroup of patients identified as having higher levels of depressive symptoms was most likely to benefit from the treatment.
Suicide risk of antidepressant medication
Over the past few years, significant concerns have been raised about the risk of suicidal thinking and behavior with the use of antidepressants in children, adolescents, and young adults. Since 2003, U.S. and European regulators have issued several public health warnings on this topic. The first such advisory issued by the U.S. Food and Drug Administration (FDA) warned about a possible association between antidepressants and suicidal thinking and behavior in children and adolescents. In December 2003, the Medicines and Healthcare Products Regulatory Agency of the United Kingdom issued a letter to doctors advising against the use of antidepressants in anyone younger than 18 years.[12]
In October 2004, the FDA mandated pharmaceutical companies to add a “black box” warning to the labeling of all antidepressants suggesting increased risk of suicidality in pediatric patients who were taking antidepressants. The FDA revised this black box warning in May 2007 to include young adults younger than 25 years.[13] The new, carefully worded warning emphasizes that the risk of suicidality is associated with both antidepressants and depression. In addition to raising concerns about increased sucidality in children, adolescents, and young adults, the warning acknowledges a significant protective effect of antidepressants in adults aged 65 and older. The meta-analysis that led to the initial black box warning in pediatric patients concluded that the antidepressants are associated with a twofold increase in suicidal ideation and behavior compared to the placebo in children and adolescents. A major meta-analysis published in the Journal of the American Medical Association reanalyzed the data from the child and adolescent studies (including seven studies not included in the initial meta-analysis), using a random-effects model. While this reanalysis found an overall increased risk of suicidal ideation/suicidal behavior consistent with the initial meta-analysis, the pooled risk differences were found to be smaller and statistically insignificant. Concerns have been raised that the unintended consequence of the warnings will be overly restricted use of antidepressants among those who benefit the most and, hence, an increase in suicidality that the warning seeks to prevent. A study examining U.S. and Dutch data suggests a drop in selective serotonin reuptake inhibitor (SSRI) prescriptions for children and adolescents since the black box warning was issued and a simultaneous increase in suicide rates in this patient population. In summary, the risk-benefit equation favors appropriate use of antidepressants with careful monitoring for suicidality. It is important to note that none of the studies that led to the black box warning included or focused on patients being treated for cancer. Clinical experience and results of small clinical trials suggest that antidepressants can be safely administered to adult cancer patients, although there are no large controlled clinical trials to support this position. When antidepressants are prescribed for patients with cancer, a careful monitoring plan should be implemented by individuals with expertise, and consultation referral should be made for patients who do not respond as anticipated or who present other concerns.
Interferon-related depression
Most antidepressant prescribing is directed at the treatment of an existing
depressive disorder or significant depressive symptoms. One study, however,
supports the use of antidepressants to prevent depression in patients receiving
high-dose interferon for adjuvant therapy of malignant melanoma.[14] The
rationale for this approach is that treatment with high-dose interferon is
associated with a particularly high rate of depression in this patient
population, and proinflammatory cytokines implicated in the biological changes
that result in depression may be directly reduced by antidepressants. In this
double-blind study of patients receiving high-dose interferon, 2 of 18 patients
in the paroxetine group developed depression during the first 12 weeks of
therapy, compared with 9 of 20 patients in the placebo group (relative risk [RR] = 0.24;
95% confidence interval [CI], 0.08–0.93). Moreover, there were significantly fewer treatment
discontinuations in the paroxetine group (5% vs. 35%, RR = 0.14; 95% CI,
0.05–0.85). Further study is required to confirm these findings and to
determine whether prophylactic use of antidepressants has benefit in
other treatment settings.
Antidepressant medication selection
The choice of antidepressant depends on a patient's medical history and
concomitant medical problems, the symptoms referable to depression, previous
responses to antidepressant medications, and the side effects associated with
the agents available.
The types of medications used to treat depression in patients with cancer
include the SSRIs, tricyclic
antidepressants (TCAs), and analeptic or CNS stimulant
agents (i.e., amphetamines). The following table outlines the commonly used
antidepressants and highlights starting dosages used in cancer patients. The Side Effects/Comments column identifies drug-specific
side effects that may be clinically advantageous or
problematic depending on the clinical situation when selecting antidepressant
medications and monitoring patients receiving these drugs. Generally, there is
a long latency period (3–6 weeks) from initiation of antidepressant
medications until the onset of a therapeutic response. In many cases,
antidepressant treatment begins at low doses followed by a period of gradual dose titration to
achieve an optimum individualized response. Initial low doses may help to
avoid initial side effects, but dose escalation may be required in order to see
therapeutic effects. For some agents, there is a therapeutic window during which
plasma concentrations correlate with a patient's antidepressant response (e.g.,
nortriptyline). For patients receiving these agents, serial drug concentration
monitoring guides therapy and facilitates providing an adequate therapeutic
trial, because plasma concentrations less than and greater than the defined
therapeutic ranges are associated with treatment failure, suboptimal responses,
and in the case of high drug concentrations, unnecessary toxicity.
Antidepressant Medications for Ambulatory Adult Patients
*Drug Class/Generic Name (Proprietary
Name)/Dosages
|
Side Effects/Comments
|
TRICYCLIC ANTIDEPRESSANTS (TCAs) |
All TCAs can cause cardiac arrhythmias. |
EKG at baseline to evaluate for preexisting
cardiac conduction abnormalities. Therapeutic
drug concentration ranges in plasma have been
identified for all agents, but dosage adjustments
should be based on a patient's clinical response
and not solely on plasma concentrations.a |
In responding patients, decrease daily dosages to
the lowest effective amount needed to sustain a
response.b TCAs can cause sexual dysfunction. |
Treatment may be associated with weight gain.c |
amitriptyline (Elavil)
|
Marked sedation; dizziness; headache; weight gain; anticholinergic effects;d orthostatic blood pressure (BP) changes (postural hypotension); may produce sexual dysfunction. Therapeutic plasma concentrations (parent drug +
active metabolite) = 110–250 ng/mL. |
|
initial: 10–25 mg as a
single daily dose,
preferably at bedtime
|
|
maintenance: 150–300 mg/day |
clomipramine (Anafranil) |
Anticholinergic effects; dizziness; drowsiness;
headache; weight gain; orthostatic hypotension. |
|
initial: 25 mg/day and gradually increase to
100 mg/day the first 2
weeks; may be given at
bedtime |
|
maintenance: 100–250 mg/day
maximum |
desipramine (Norpramin) |
Mild sedation; increased appetite; nausea;
minimal anticholinergic effects;d orthostatic BP changes.
Therapeutic plasma concentrations = 125–300 ng/mL. |
|
initial: 25–50 mg/day as a single daily dose, preferably at bedtime |
|
maintenance: 100–300 mg/day
as a single daily dose; In elderly patients, daily
doses >150 mg are not
recommended |
doxepin (Sinequan)
|
Moderately to very sedating; dizziness; headache; weight gain; moderate anticholinergic effects;d postural hypotension. Optimal antidepressant effect is characteristically delayed by 2–3 weeks; however, onset of antianxiety effect is comparatively rapid.
Therapeutic plasma concentrations (parent drug +
active metabolite) = 100–200 ng/mL. |
|
initial: 10–25 mg/day as
a single daily dose,
preferably at bedtime
|
|
maintenance: 75–300 mg/day
as a single daily dose,
preferably at bedtime |
imipramine (Tofranil) |
Moderately to very sedating; dizziness; headache; weight gain; moderate anticholinergic effects;d moderate-marked orthostatic BP changes; may produce sexual dysfunction (both genders). Therapeutic plasma concentrations (parent drug + active metabolite) = 200–350 ng/mL. |
|
initial: 25–50 mg/day as
a single daily dose,
preferably at bedtime |
|
maintenance: 75–200 mg/day
as a single daily dose,
preferably at bedtime |
nortriptyline (Pamelor, Aventyl) |
Mild-moderate sedation; constipation; nausea; increased appetite; mild-moderate anticholinergic effects;d the TCA least likely to produce postural hypotension. Therapeutic plasma concentrations = 50–150 ng/mL. |
|
initial: 10–25 mg, 3–4
times daily
|
|
maintenance: 30–50 mg, 3
times daily, daily doses >150 mg are
not recommended |
SELECTIVE SEROTONIN
REUPTAKE INHIBITORS
(SSRIs)
|
SSRIs have few anticholinergic and cardiovascular adverse effects. Life-threatening and fatal reactions have
occurred in patients who receive SSRIs within 2 weeks of using monoamine oxidase inhibitor
antidepressants. Sexual dysfunction has been reported to be associated with
SSRI use.
There is limited experience with long-term use.
|
citalopram (Celexa) |
Ejaculation disorder; other sexual dysfunctions; insomnia; dry mouth; nausea;
somnolence. In vitro studies indicated that
CYP3A4 and CYP2C19 are the primary enzymes
involved in the metabolism of citalopram.
Citalopram is a relatively weak inhibitor of
CYP2D6. |
|
initial: 10 mg/day |
|
maintenance: 10–40 mg/day |
fluoxetine (Prozac) |
Anxiety; nervousness; insomnia; anorexia; mild
bradycardia; sinoatrial node slowing; weight loss; solar
photosensitivity; hyponatremia; sexual
dysfunction; may alter glycemic
control in diabetic patients.
Fluoxetine substantially inhibits CYP2D6 and may
inhibit the clearance of other drugs metabolized
by cytochrome P450 CYP2D6 isozymes.[15]
Fluoxetine probably inhibits CYP2C9/10,
moderately inhibits CYP2C19, and mildly inhibits
CYP3A4;[15] fluoxetine metabolism is impaired
in elderly patients. |
|
initial: 10–20 mg/day |
|
maintenance: 20–80 mg/day |
escitalopram (Lexapro) |
Nausea, vomiting, diarrhea, constipation, upset stomach, loss of appetite, dizziness, drowsiness, trouble sleeping, back pain, or dry mouth. |
|
initial: 10 mg/day |
|
maintenance: 10–20 mg/day |
fluvoxamine (Luvox)
|
Nausea; sexual dysfunction; headache; nervousness; insomnia; drowsiness. |
|
initial: 50 mg at bedtime,
adjust in 50 mg increments
at 4- to 7-day intervals |
|
maintenance: 100–300 mg/day |
paroxetine (Paxil) |
Anxiety; nervousness; insomnia; mild weight loss;
headache; solar photosensitivity; hyponatremia;
sexual dysfunction.
Paroxetine substantially inhibits and may
interact with other drugs metabolized by
cytochrome P450 CYP2D6 isozyme.[15]
Paroxetine metabolism is impaired in elderly
patients.
|
|
initial: 10–20 mg/day |
|
maintenance: 20–50 mg/day |
sertraline (Zoloft) |
Anxiety; nervousness; insomnia; mild weight loss;
headache; solar photosensitivity; hyponatremia;
sexual dysfunction.
Produces mild inhibition of and may interact with
drugs metabolized by cytochrome P450 CYP2D6
isozymes with little, if any, effect on CYP1A2,
CYP2C9/10, CYP2C19, or CYP3A3/4.[15] |
|
initial: 25–50 mg/day |
|
maintenance: 50–200 mg/day |
MONOAMINE OXIDASE INHIBITORS
(MAOIs) |
|
tranylcypromine (Parnate) |
Orthostatic hypotension; drowsiness; hyperexcitability; headache. Low tyramine diet required. |
|
initial: 10 mg twice daily,
increase by 10 mg
increments at 1- to 3-week
intervals
|
|
maintenance: 10–40 mg/day |
phenelzine (Nardil) |
Orthostatic hypotension; drowsiness; hyperexcitability; headache. Low tyramine diet required. |
|
initial: 15 mg 3 times
a day
|
|
maintenance: 15–90 mg/day |
selegiline (EMSAM) |
Application site reaction; orthostatic hypotension; diarrhea; headache; insomnia; dry mouth. Any dosages higher than 6 mg/24 h require low-tyramine diet. |
|
initial: 6-mg patch/24 h (20-mg patch topically every 24 h) |
|
maintenance: 6-mg patch/24 h (20-mg patch topically every 24 h). May increase at increments of 3 mg/24 h at 2-week intervals up to 12 mg/24 h. |
ATYPICAL ANTIDEPRESSANTS |
In general, serum drug concentrations do not
correlate with antidepressant response. |
bupropion (Wellbutrin, also approved for the treatment of smoking cessation as Zyban) |
Initially activating dose-related seizure-inducing potential; contraindicated in patients with CNS involvement,
with a history of seizure, in those with
concomitant conditions predisposing to seizure,
and in patients taking other drugs that lower
seizure threshold. Mild-moderate sedation; mild-moderate
anticholinergic effects;d mild orthostatic BP
changes; agitation; insomnia; headache;
confusion; dizziness; seizures; weight loss. |
|
initial: 75 mg/day |
|
maintenance: 200–450 mg/day not to exceed 150 mg/dose |
trazodone (Desyrel) |
Mild-moderate sedation; negligible
anticholinergic effects; mild-moderate
orthostatic BP changes, particularly in elderly
patients; dizziness; headache; confusion; muscle
tremors; may produce priapism; taking trazodone with
food can decrease gastrointestinal upset.
Therapeutic plasma concentrations = 800–1,600
ng/mL.
|
|
initial: 50 mg/day |
|
maintenance: 150–600 mg/day |
nefazodone (Serzone) |
Postural hypotension (although <TCAs); less
sexual dysfunction than is
reported with SSRIs. Headache; drowsiness;
insomnia; agitation; confusion; nausea; tremor.
Potential interaction with drugs metabolized by
cytochrome P450 isozymes, CYP2D6 and CYP3A4.
Check liver function tests at baseline and
periodically during therapy. May cause fatal
hepatotoxicity. |
|
initial: 100 mg twice daily |
|
maintenance: 300–600 mg/day |
mirtazapine (Remeron) |
A tetracyclic antidepressant.
Mirtazapine elimination is decreased in elderly
persons.
Somnolence; dizziness; increased appetite and
weight gain; constipation; hypertension; edema;
confusion; increased nonfasting triglycerides
and cholesterol; significantly increased hepatic
ALT; orthostatic hypotension.
When used concomitantly with drugs that reduce
the seizure threshold (e.g., phenothiazines),
mirtazapine may increase the risk of seizure. |
|
initial: 7.5–15 mg/day |
|
maintenance: 15–45 mg/day |
venlafaxine (Effexor) |
Dose-related sustained hypertension. Headache;
dizziness; insomnia; nausea; constipation;
abnormal ejaculation.
Life-threatening and fatal reactions have
occurred in patients who received venlafaxine
within 2 weeks of using monoamine oxidase
antidepressants. |
|
initial: 75 mg/day |
|
maintenance: 150–375 mg/day |
duloxetine (Cymbalta) |
Nausea, dry mouth, constipation, decreased appetite, fatigue, sleepiness, and increased sweating; decreased sexual drive or ability; urinary hesitation. |
|
initial: 30 mg/day |
|
maintenance: 30–60 mg/day |
Psychostimulants |
Psychostimulants may cause restlessness,
agitation, insomnia, nightmares, psychosis,
anorexia; and may exacerbate preexisting cardiac
disease.
Psychostimulants should be administered early in a
patient's daily waking cycle. Psychostimulants are sometimes used adjuvantly to
antagonize opioid analgesics' sedative effects. |
dextroamphetamine (Dexedrine) |
Drug tolerance, abuse, and dependence liability.
Arrhythmia; nervousness; restlessness;
insomnia. Contraindicated in patients with
advanced arteriosclerosis, symptomatic
cardiovascular disease, moderate-severe
hypertension, and glaucoma. |
|
initial: 2.5–5 mg/day |
|
maintenance: 10–30 mg/day |
methylphenidate (Ritalin, Methylin) |
Drug tolerance, abuse, and dependence liability.
Hypertension; may decrease the convulsive
threshold in patients with a history of seizure
disorders. Tachycardia; nervousness; insomnia;
anorexia; drowsiness; dizziness. |
|
initial: 2.5–10 mg/day |
|
maintenance: 20–60 mg/day |
dexmethylphenidate (Focalin) |
Dry mouth,
tremor or muscle spasms,
nervousness,
trouble sleeping,
headache, drowsiness,
nausea,
insomnia,
increased sweating,
dizziness, lightheadedness,
changes in sexual function. |
|
initial: 10 mg/day |
|
maintenance: 10–20 mg/day |
*Consult complete prescribing information for appropriate administration
schedules.
|
Notes:
|
aTCAs prolong cardiac conduction through His-Purkinje system similar to
Type IA antiarrhythmic agents (e.g., quinidine). They are specifically
contraindicated in patients with bundle-branch disease and second- or
third-degree heart block. Their effects on conduction correlate with dosage
and serum concentrations and for those agents with positive chronotropic and
adrenergic-stimulating properties, TCAs can cause reentry arrhythmias.
Persons at greatest risk are those with preexisting cardiac conduction
defects and those who have taken an overdose.
|
bPlasma concentrations are most useful for guiding treatment in elderly
patients who are (1) experiencing signs and symptoms of toxicity, (2)
unresponsive to treatment, (3) suspected of being noncompliant with planned
treatment, or (4) receiving other medications that may interact or otherwise
alter antidepressant medication pharmacokinetics.
|
cTCAs and other antidepressants may cause sexual dysfunction characterized
as decreased libido, penile erectile dysfunction, and decreased sensation
during orgasm and ejaculation. Management consists of waiting for spontaneous
resolution with continued therapy, decreasing the antidepressant dose,
selecting an alternative antidepressant, or concomitant treatment with
medications that treat the dysfunction (e.g., bethanechol for antidepressants
with prominent anticholinergic effects).
|
dCommon antimuscarinic or anticholinergic effects include dry mouth,
blurred vision, constipation, and urinary retention. Although patients may
eventually develop tolerance to these effects with repeated medication use,
symptoms may not completely resolve until the drug is discontinued.
|
When selecting an antidepressant drug, it is worthwhile to consider that
side effects may have a clinical advantage. For example, some
TCAs, such as amitriptyline, and atypical antidepressants, such as mirtazapine and trazodone, produce
sedation and may be useful for agitated patients and for those who have
difficulty getting to sleep. Consequently, treatment is often initiated as a
single daily dose administered at bedtime. Although most patients will develop
tolerance to antidepressants' sedative effects with continued treatment, the
need for soporific agents may diminish with improvement in depressive symptoms.
When selecting antidepressants, either singly or in combination, consider the following:
- Target specific distressing symptoms.
- Evaluate coexistent medical problems that may be exacerbated by particular
antidepressants.
- Minimize side effects and avoid worsening of current health status.
- Determine the patient's ability to swallow solid dosage forms; he or she may be able to take an antidepressant in liquid form (e.g., amitriptyline, nortriptyline, doxepin,
fluoxetine). Alternatively, some antidepressants are available as parenteral
dosage forms (e.g., amitriptyline and imipramine injection).
- Evaluate the patient's medication profile for potential interactions with
antidepressant drugs.
Selective serotonin reuptake inhibitors
The postulated mechanism of action of SSRIs involves the blockade of serotonin neuronal reuptake, leading to desensitization of serotonergic feedback receptors. All currently available SSRIs are equally efficacious; they differ primarily in their safety, tolerability, half-lives, and drug-drug interactions. While some side effects are more common with some SSRIs than with others, side effects and tolerability may differ significantly in individual patients. SSRIs have become the first-line treatment for depressive disorders, owing to their better tolerability side effect profile, especially in comparison with the TCAs. As discussed earlier, antidepressant studies conducted in patients with cancer are done mostly with SSRIs or TCAs. None of the clinical trials have included or focused on children and adolescents being treated for cancer.[16-19] Overall, the evidence on the efficacy of SSRIs for treating cancer-related depression remains limited, and more studies are needed to address the efficacy, safety, tolerability, and drug-drug interaction issues in the context of cancer and cancer treatments. The British Committee on Safety of Medicines considered only one of the SSRIs (fluoxetine) to have a favorable balance of risks and benefits, but it is only considered beneficial in approximately one in ten patients.[20] Consistent with this finding, age-stratified analyses of the child and adolescent studies found that for children younger than 12 years with major depression, only fluoxetine showed benefit over placebo.[21] As noted, none of the children or adolescents in these studies had cancer, so there are no reports available that address whether there are additional increased risks of adverse events associated with the use of SSRIs following exposure to different chemotherapeutic agents and/or central nervous system (CNS) radiation treatment. Frontline, alternative, effective, behavioral, and pharmacologic treatments for depression should be used for children and adolescents being treated for cancer. However, if the risks of depression are significant and SSRIs are considered, consultation from a child psychiatrist or neurologist is essential, and close monitoring of potential adverse events is crucial. No warning has been issued for adult use of SSRIs.
Discontinuation of antidepressants
The optimal duration of antidepressant therapy for patients treated for depressive
symptoms (without a depressive disorder) is unknown. Patients with a
depressive disorder who achieve a beneficial response to
antidepressant pharmacotherapy should continue treatment for a minimum of 4 to
6 months after depression resolves. When patients are discontinuing antidepressant
medications, TCA doses should be tapered by approximately 25% per week to avoid
cholinergic rebound (e.g., hypersalivation, diarrhea). In patients who
experience intolerable adverse effects, however, doses may be tapered quickly.
With the exception of fluoxetine, gradual tapering is advised when decreasing
doses or discontinuing treatment for all SSRIs. Other antidepressants with
short half-lives, such as venlafaxine, also should be tapered gradually.
Withdrawal symptoms, both somatic and psychological, frequently emerge after
abrupt discontinuation, during intermittent noncompliance, and sometimes during
dose reduction; though these symptoms are generally mild, short-lived, and
self-limiting, they can be distressing and may lead to missed workdays and
decreased productivity. Mild symptoms can often be treated by reassuring a
patient that they are usually transient. For more severe symptoms, it may be
necessary to reinstate the dosage of the original antidepressant and slow the
rate of taper. Symptoms of discontinuation may be mistaken for physical
illness or relapse into depression and misdiagnosis may lead to unnecessary,
costly tests and treatment. Thus, health care professionals need to be
educated about the potential adverse effects of SSRI discontinuation.[22]
Side effects
TCAs can produce abnormal myocardial conduction; thus, a cardiac history and a
recent EKG should be obtained in patients with a history of cardiac problems.
Many tricyclic antidepressants have a sedating effect; therefore, treatment
typically is started at low doses at bedtime. The main exception is
desipramine, which some patients find mildly stimulating and can be administered
in the morning to reduce insomnia, if it develops. Daily doses are increased
slowly every few days or at weekly intervals until symptoms improve. Many
patients become tolerant to the drugs' sedative effects, and total daily doses
may be divided and given during patients' waking cycles.
TCAs are still regarded as first-line agents for severe, major
depression; however, SSRI use is increasing for that indication because of the
effectiveness of SSRIs and the low risk of clinically significant side effects that are
associated with TCAs, such as cardiac arrhythmias, hypotension, and
anticholinergic effects. In addition, TCAs are highly toxic on overdose. Side
effects commonly associated with the SSRIs include nausea, vomiting, diarrhea,
somnolence, insomnia, headache, confusion, dizziness, asthenia, and sexual
dysfunction. Drug-specific adverse effects associated with fluoxetine include
gastric distress, brief periods of anxiety or agitation, and anorgasmia in
females. Treatment with sertraline is sometimes complicated by dyspepsia,
tremor, and ejaculatory delay in men.
The pharmacokinetic profiles of SSRIs permit them to be given once a day,
thus improving patient compliance.[23] Sertraline and paroxetine have a
half-life of approximately 20 hours; thus, steady-state systemic concentrations
can be achieved within 1 week after starting treatment and altering dosage or
administration schedules. In comparison, repeated dosing appears to inhibit
fluoxetine metabolism; consequently, both fluoxetine and its active
metabolite, norfluoxetine, may be present in the body for weeks after
discontinuing treatment.
Drug-drug interactions
Clinicians who prescribe and monitor patients receiving antidepressants should
also become familiar with their potential for interactions with other
medications.[24] The SSRIs venlafaxine, nefazodone, and mirtazapine are
metabolized by cytochrome P450 enzymes; their pharmacokinetics may be altered,
or they may affect the clearance of drugs metabolized by the same enzymes.
Marked differences exist, however, between the SSRIs and SSRI metabolites with
regard to their effects on specific cytochrome P450 enzymes.[15] For example,
both fluoxetine and norfluoxetine inhibit CYP3A4 isoenzyme; however, the
metabolite is more potent than fluoxetine and in view of its longer half-life
the potential for interactions may persist for weeks after fluoxetine is
discontinued.[25] Understanding the similarities and differences in their
pharmacology can aid clinicians in using these agents optimally and avoiding
clinically important pharmacokinetic drug-drug interactions. In addition,
since all SSRIs are highly protein-bound to albumin (± alpha-1 acid
glycoprotein), clinicians must consider their potential for interactions with
other highly protein-bound medications. Sertraline and paroxetine may be
preferred in patients with renal or hepatic dysfunction since they are
metabolized and excreted as inactive compounds.[26]
Atypical antidepressants
-
Bupropion
Bupropion is a unique alternative to tricyclics and SSRIs for treating persons
with depression and cancer, especially when depression is accompanied by
fatigue. Pharmacologically, bupropion is a weak inhibitor of monoamine
reuptake and demonstrates a slight preference for dopamine transport
inhibition; however, it may be metabolically converted to active substances
with amphetamine-like activity that affect both dopamine and norepinephrine
reuptake. Bupropion generally does not cause sexual dysfunction; therefore, it
may be useful in treating patients who wish to remain sexually active and those
who have experienced sexual dysfunction with other antidepressants. Bupropion
treatment is initiated with doses of 75 mg once daily, preferably in the early
part of the day. Patients may initially require a moderate- to long-acting
sedative/hypnotic drug at bedtime for the insomnia, agitation, and motor
restlessness sometimes associated with bupropion. Risk of seizure with
bupropion may be as much as 4 times greater than is associated with other
antidepressants. Single doses should not exceed 150 mg, a dose increase should
not be greater than 100 mg of bupropion per day, and dose increases should be
gradual—at least 3 days after a previous increase in dose. Because the risk of
seizure markedly increases in patients receiving bupropion at doses between
450 mg and 650 mg, the total daily dose should not exceed 450 mg. Bupropion is
contraindicated in patients with malignant diseases involving the brain and
with a history of cranial trauma or seizure disorder [27] and in persons with a
history of bulimia.[28]
-
Venlafaxine
Venlafaxine affects both norepinephrine and serotonin reuptake and enhances
serotonin neurotransmission.[29] Venlafaxine does not produce the same
uncomfortable antimuscarinic and antiadrenergic side effects as the TCAs;
however, it does produce side effects similar to the SSRIs, particularly
nausea, headache, somnolence, and dry mouth. In some patients, venlafaxine may
cause sustained increases in blood pressure; blood pressure should therefore be
evaluated before treatment is started, monitored after treatment
is initiated, and monitored after doses are increased. Venlafaxine is given twice a day, with food.
-
Trazodone and nefazodone
The primary actions of the atypical antidepressants trazodone and nefazodone
are not well established. Although they both antagonize serotonin reuptake,
they are many times weaker in this respect compared with SSRIs. Trazodone is
active, and both agents are metabolized to compounds that have agonistic
activity at some serotonin receptors (5-HT1). Both agents may have additional
active metabolites that contribute to their clinical activity.[29] Nefazodone
is reported to be useful in patients with agitated depression and may be better
tolerated than the SSRIs. Nefazodone can complicate some patients' management
because it is a potent inhibitor of hepatic cytochrome P450 3A4 isoenzymes. Its
use is, therefore, relatively contraindicated in patients who are receiving
methadone and absolutely contraindicated in those receiving terfenadine or astemizole.
-
Mirtazapine
There is growing clinical experience with mirtazapine in persons with cancer.
Pharmacologically, mirtazapine is a noradrenergic and specific serotonergic
antidepressant. It competitively antagonizes presynaptic alpha-adrenergic
receptors (alpha2) and serotonin receptors (5-HT2 and 5-HT3), the net result of
which enhances norepinephrine release and noradrenergic neurotransmission.[29,30]
Sedation is
the predominating side effect at subtherapeutic low doses (<15 mg/day), and anecdotal evidence suggests that sedation decreases at higher
doses. Its side-effect profile also includes increased appetite, which may
cause weight gain, dizziness, dry mouth, and constipation.[31] Although it
is a structural analog of mianserin (an antidepressant that is marketed in
Europe), mirtazapine has rarely been implicated in producing severe
blood dyscrasias, including agranulocytosis, as has mianserin.[32] Little is
known about mirtazapine interactions with other drugs, but it is thought to
have a lesser risk of clinically significant drug interactions than SSRIs.[33]
The initial dose for mirtazapine is 15 mg per day given at bedtime. Doses may
be increased at intervals not less than 1 to 2 weeks, up to a maximum daily dose
of 45 mg.
Benzodiazepines
Benzodiazepines can be used to effectively treat the anxiety that may be
associated with depression. In patients receiving antidepressant medications
and benzodiazepines concomitantly, the latter drugs may be discontinued after
patients' depressive symptoms begin to abate; however, both agents can be
continued safely if needed. Benzodiazepines should never be stopped abruptly
because withdrawal symptoms with possible seizures may occur. The dose of
benzodiazepines should be tapered slowly at a rate of approximately 25% every 3
to 4 days.
Psychostimulants
Clinical experience suggests that analeptic agents (e.g., methylphenidate
and dextroamphetamine) are useful at low doses for patients whose
symptoms include depressed mood, apathy, decreased energy, poor concentration,
and weakness.[34] They are particularly useful for patients with advanced cancer who have a limited life expectancy (weeks to a few months). Compared with traditional antidepressants such as the TCAs and SSRIs that take 3 to 4 weeks to take effect, the psychostimulants often demonstrate antidepressant effects within a few days of starting treatment. They promote a sense of well-being, decreased fatigue, and
increased appetite. Analeptic agents can be helpful in countering the sedating effects of
opioids, and in comparison with antidepressants, they are rapidly effective.
Adverse effects associated with analeptic agents include insomnia, euphoria,
and mood lability. High doses and long-term use may produce anorexia,
nightmares, insomnia, euphoria, or paranoia.
Methylphenidate and dextroamphetamine are administered in divided
doses early in a patient's waking cycle to avoid sleep disturbances, e.g.,
insomnia and nighttime arousal. Like benzodiazepines, these medications are
adjuncts to antidepressant medications; they may be started concomitant with an
antidepressant and discontinued when depressive symptoms abate.[35,36]
Clinical Trials of Psychostimulants in Cancer Patients
Study
|
Comments
|
Drug(s)
|
Outcome
|
Meyers et al. 1998 [37] |
Brain tumor; N = 30 |
methylphenidate (Ritalin) |
↑ mood, ↑ cognition, ↑ function |
Olin and Masand 1996 [38] |
Mixed cancer; N = 59; chart review |
dextroamphetamine (Dexedrine); methylphenidate (Ritalin) |
↓ depression, ↑ appetite |
Bruera et al. 1992 [39] |
Cancer pain vs. opioid infusion; N = 20 |
methylphenidate (Ritalin); placebo |
↑ cognition, ↓ sedation |
Fernandez et al. 1987 [36] |
Mixed cancer; rapid onset; N = 30 |
methylphenidate (Ritalin;up to 80 mg) |
↓ depression |
Bruera et al. 1986 [40] |
Pain; double-blind cross-over study; N = 24 |
mazindol (Mazanor) |
↓ pain, ↓ appetite, no effect on mood
|
Joshi et al. 1982 [41] |
Terminally ill |
amphetamine |
↑ comfort |
Monoamine oxidase inhibitors
The use of monoamine oxidase inhibitors (MAOIs) in the cancer population has
been limited because the nutritional requirements of a
tyramine-free diet are generally more difficult to accomplish in patients
receiving antineoplastic treatments. MAOIs are contraindicated in
patients receiving opioids, sympathomimetics, and procarbazine because of the
potential for developing hypertensive crisis.
MAOIs may cause adverse reactions when taken with other medications and certain
foods. MAOIs impair the metabolism of morphine and other opioids as well as
barbiturates and may lead to exaggerated ventilatory depression. Meperidine HCl (Demerol), an opioid, has been associated with
hypertension, hyperpyrexia, skeletal muscle rigidity, seizures, and coma when used with MAOIs.[42]
Exaggerated effects of antihistamines, anticholinergics, and tricyclic
antidepressants may be secondary to impaired metabolism by MAOIs. In addition,
the hypoglycemic effects of insulin and oral sulfonylureas may be potentiated
by MAOIs.
MAOIs may also interact with specific anesthetic drugs used during surgery.[43]
Cancer patients in particular may frequently undergo surgical procedures and
should alert their anesthesiologist of all medications. Postoperative pain
should not be treated with meperidine HCl. MAOIs should neither be taken with
procarbazine, a chemotherapeutic agent used in the treatment of lymphomas and
brain tumors, nor used with other antidepressants.
The U.S. Food and Drug Administration (FDA) has recently approved a transdermal antidepressant that may have particular value in the treatment of the depressed cancer patient who is unable to swallow or take medications by mouth. The antidepressant selegiline (sold under the trade name EMSAM) is an irreversible MAOI. To date, the drug has not been evaluated for the treatment of depression in cancer patients.
Many of the usual dietary restrictions (low-tyramine diet) and drug-drug interactions (the product should not be used with meperidine, propoxyphone, or methadone) are germane to selegiline (see table below). However, according to the package insert, the 20-mg skin patch (which delivers 6 mg of selegiline in a 24-hour period) can be used without the dietary restrictions found on all MAOIs marketed to date. This recommendation is supported by clinical trials and other evidence submitted to the FDA. The two higher doses (a 30-mg patch that delivers 9 mg in 24 hours and a 40-mg patch that delivers 12 mg in 24 hours) carry the usual dietary warning. This drug has not been evaluated in cancer patients for safety and efficacy.
Tyramine-Containing Foods*
Class of Food and Beverage
|
Tyramine-Rich Foods and Beverages To Avoid
|
Acceptable Foods Containing Little or No Tyramine
|
Meat, poultry, and fish |
Air-dried, aged, and fermented meats, sausages, and salamis (including cacciatore, hard salami, and mortadella); pickled herring; and any spoiled or improperly stored meat, poultry, and fish (e.g., foods that have undergone changes in color or odor or that have become moldy); spoiled or improperly stored animal livers |
Fresh meat, poultry, and fish, including fresh processed meats (e.g., lunch meats, hot dogs, breakfast sausage, and cooked sliced ham) |
Vegetables |
Broad bean pods (fava bean pods) |
All other vegetables |
Dairy |
Aged cheeses |
Processed cheeses, mozzarella, ricotta cheese, cottage cheese, and yogurt |
Beverages |
All varieties of tap beer, and beers that have not been pasteurized so as to allow for ongoing fermentation |
As with other antidepressants, concomitant use of alcohol with selegiline is not recommended. (Bottled and canned beers and wines contain little or no tyramine.) |
Miscellaneous |
Concentrated yeast extract (e.g., Marmite), sauerkraut, most soybean products (including soy sauce and tofu); OTC supplements containing tyramine |
Brewer’s yeast, baker’s yeast, soy milk, commercial chain-restaurant pizzas prepared with cheeses low in tyramine |
OTC = over-the-counter.
|
*Adapted from the EMSAM Medication Guide.[44] The foods and beverages listed above should be avoided beginning on the first day of treatment with selegiline 9 mg/24 h or 12 mg/24 h and should continue to be avoided for 2 weeks after a dose reduction to 6 mg/24 h or following the discontinuation of selegiline 9 mg/24 h or 12 mg/24 h.
|
Selegiline is a nonselective MAOI, inhibiting not only the MAO-B enzyme in the central nervous system but also MAO-A elsewhere in the body. In the digestive tract, MAO-A normally metabolizes tyramine, a dietary amine that is found in high concentrations in foods such as aged cheese and red wine. The breakdown of tyramine in the gut prevents significant amounts of it from being absorbed and circulated throughout the body. Tyramine is a potent pressor—leading to constriction of blood vessels—which ultimately results in increased blood pressure. Large amounts of tyramine can lead to hypertensive crises, resulting in stroke, heart attack, and even death. Because the medication is absorbed from the skin patch and bypasses the gut wall, it is thought that transdermal selegiline will have a significantly reduced effect on MAO-A in the digestive tract. In addition, at lower doses, selegiline is thought to inhibit MAO-B preferentially, while at higher doses both A and B isoenzymes are affected. With significantly reduced inhibition of digestive tract MAO-A, dietary restrictions are not considered necessary for the lower dose. In considering starting this drug, consult with a pharmacist about multiple classes of drug-drug interactions. This drug has not been evaluated in people with cancer.[45]
Foods that contain large amounts of tyramine, such as cheese, chicken liver,
chocolate, beer, and wine, may provoke hypertension (initially manifesting as
headache) and cardiac dysrhythmias.
St. John's wort
There has been much interest in the use of St. John's wort (SJW, Hypericum
perforatum) as an herbal antidepressant. Its use has become widely advertised
as an over-the-counter supplement for mood enhancement.
In the United States, dietary supplements are regulated as foods, not drugs.
Premarket approval by the FDA is not required
unless specific disease prevention or treatment claims are made, which is often
not the case with SJW. Because a review for manufacturing consistency is not required for dietary supplements and no specific
standards for dose or purity exist, there may be considerable variation from
lot to lot for all products marketed as dietary supplements, including SJW.
Promotional statements about SJW may address mood enhancement and positive
outlook. It may be found as a stand-alone supplement or in combination with
other herbs, vitamin and mineral supplements, or food products such as
teas. The FDA issued a warning highlighting the results from a study conducted
by the National Institutes of Health that showed a significant drug
interaction between SJW and indinavir, a protease inhibitor used to treat HIV
infection. In this study, concomitant administration of SJW and indinavir
substantially decreased indinavir plasma concentrations, potentially due to
induction of the cytochrome P450 metabolic pathway.[46]
While its specific mechanisms of action are unclear, there are 3 presumed
active compounds in the herb. One of these compounds is a mild MAOI (see above
precautions). Historically, prescription MAOIs have been used to treat
depression as well as Parkinson disease, narcolepsy, and occasionally
hypertension, but they are rarely used today. The side effects of SJW include dry
mouth, dizziness, gastrointestinal (GI) distress, fatigue, and confusion.
A randomized double-blind placebo-controlled trial involving 200 adult
outpatients with major depressive disorder compared the safety and efficacy of
SJW with placebo. This study was designed to address the numerous methodological
flaws in the existing literature [47] that served as the basis for the
meta-analysis that had concluded that SJW is significantly superior to
placebo.[48] This study represents the first report of a large-scale
randomized placebo-controlled trial of SJW in the United States. This study
does not support significant antidepressant or antianxiety effects of SJW.
Specifically, compared with placebo, there were no significant differences in
response rates in the overall sample of outpatients with major depression.
On the basis of these trial data indicating lack of efficacy in depressed patients in
primary care settings, as well as the lack of properly designed positive trials
in cancer patients, SJW should not be recommended for major depression in
cancer patients.
Antidepressant effects
The following tables highlight tips that may be useful in determining what
medication is best to use for a particular patient. The tables focus on the
effects these medications may have beyond their antidepressant effects that may
decrease or increase patient distress, such as fatigue, insomnia, and nausea
and vomiting.
Physical Symptom- and Distress-Driven Approach to
Choosing an Antidepressant in Adult Cancer Patients
Distressing Symptom
|
SSRI
|
TCA
|
Psychostimulants
|
Other
|
Fatigue |
+ (a) |
|
+ |
+ (a) |
Insomnia (b) |
|
+ |
|
+ (b) |
Neuropathic pain (c) |
+ |
+ |
|
|
Opioid side effects |
+ |
|
+ |
|
Constipation |
+ |
|
+ |
|
Loss of appetite
(weight loss) |
|
+ |
+ |
|
Anxiety |
+ |
+ |
|
+ (d) |
Dry mouth/stomatitis |
+ |
- |
+ |
|
Key:
|
(-) use of this medication could worsen the symptom
|
(+) use of this medication could relieve the symptom
|
Notes:
|
(a) Although all SSRIs have the potential paradoxical side effect of
hypersomnia, fluoxetine is particularly activating. Bupropion is also somewhat
activating.
|
(b) Sedating antidepressants are useful for insomnia, either alone or in
addition to another antidepressant. Trazodone and mirtazapine are often used as sleep aids in
combination with another antidepressant.
|
(c) Some antidepressants are useful in treating neuropathic pain. The most
studied of these are the TCAs, particularly amitriptyline.
|
(d) Sedating antidepressants are most useful for anxious/agitated patients.
These include the TCAs, trazodone, mirtazapine, and nefazodone.
|
SSRI = Selective Serotonin Reuptake Inhibitor
|
TCA = Tricyclic Antidepressant
|
In general, doses should start low and increase slowly. This list does not
indicate absolute indications or contraindications for particular medications.
A current Physicians' Desk Reference or another reliable drug information
resource and experience should guide clinical decision making.
|
Factors to Consider in Choosing an Antidepressant
For Adult Cancer Patients
Comorbid Medical Conditions
|
SSRI
|
TCA
|
Psychostimulants
|
Other
|
Cardiac history |
+ |
- |
|
+ (a) |
Hepatic dysfunction |
+ (b) |
+ |
- |
|
Renal dysfunction (c) |
|
|
|
|
Glaucoma |
+ |
- (d) |
|
|
Neuropathic pain |
+ |
+ |
|
|
Key:
|
(-) use of this medication may be a less appropriate choice
|
(+) use of this medication could relieve the symptom
|
Notes:
|
(a) In general, TCAs and psychostimulants can cause and exacerbate cardiac
arrhythmia. SSRIs, bupropion, venlafaxine, and nefazodone are generally less
likely to cause cardiac problems. EKGs should be obtained before starting TCA
medication, and a cardiologist should be consulted if there is concern for
cardiac compromise.
|
(b) The shorter-acting SSRIs (sertraline and paroxetine) are less problematic
than fluoxetine in patients with hepatic dysfunction. There is less potential
for adverse drug interactions and fewer problems related to drug accumulation
due to a shorter half-life. Sertraline and nefazodone reportedly have less
effect on hepatic P450 enzyme activity.
|
(c) Clinicians should consider whether antidepressant doses and administration
schedules require modification for their patients with renal or hepatic
insufficiency.
|
(d) The TCAs are contraindicated in closed-angle glaucoma.
|
It should be noted that electroconvulsive therapy (ECT) is a useful and safe
therapy when other interventions have not succeeded in relieving the depressive
syndrome that may represent a life-threatening complication of treatable
cancer.[49,50] Experience is limited, however, in using ECT in patients
receiving mirtazapine and trazodone, and there are no clinical studies
establishing the use of ECT in patients receiving SSRIs. Prolonged seizures
have occurred rarely in patients receiving fluoxetine.
Psychotherapy
Overview
Traditionally, depressive symptomatology was managed with insight-oriented
psychotherapy, which is quite useful for some people with cancer. For many
other people, these symptoms are best managed with some combination of crisis
intervention, brief supportive psychotherapy, and cognitive-behavioral
techniques.
Psychotherapy for depression has been offered in a variety of forms. Most interventions have been time limited (ranging between 4 and 30 hours), have been offered in both individual and small-group formats, and have included a structured educational component about cancer or a specific relaxation component.[51]
Cognitive-behavioral psychotherapy has been one of the most prominent types of therapies studied in recent investigations. Cognitive-behavioral interventions focus on altering specific coping strategies aimed at improving overall adjustment and typically focus on specific thoughts and their relationship to emotions and behaviors. Understanding and altering one’s thoughts can change emotional reactions and accompanying behaviors. For example, frequent, intrusive, uncontrollable thoughts about loss, life changes, or death can cause poor concentration and precipitate feelings of sadness, guilt, and worthlessness. In turn, these feelings can result in increased sleep, withdrawal, and isolation. A cognitive-behavioral intervention focuses on the intrusive thoughts, often challenging their accuracy or rationality and noting specific patterns of cognitive distortions. Simultaneously, patients develop specific cognitive coping strategies that are designed to alter emotional reactions and accompanying behaviors. The end result is improved coping, enhanced adjustment, and better overall quality of life.
Other goals of psychotherapy include enhancing coping skills, directly reducing distress, improving problem-solving skills, mobilizing support, reshaping negative or self-defeating thoughts, and developing a close personal bond with a knowledgeable, empathic health care provider.[52-56] Consultation with a cleric or a member of a pastoral care department may also help some individuals.
Specific goals of these therapies include the following:
- Assist people with cancer and their families by answering questions about the illness and its treatment, clarifying information, correcting misunderstandings, giving reassurance, and normalizing responses to the illness and its effect on their families. Explore the present situation with the patient and how it relates to his or her previous experiences with cancer.
- Assist with problem solving, bolster the patient’s usual adaptive defenses, and help the patient and family develop further supportive and adaptive coping mechanisms. Identify maladaptive coping mechanisms and assist the family in developing alternative coping strategies. Explore areas of related stressors (e.g., family role and lifestyle changes), and encourage family members to support and share concerns with each other.
- When the focus of treatment changes from cure to palliation, reinforce strongly that, though curative treatment has ended, the team will aggressively treat symptoms as part of the palliation plan; the patient and family will not be abandoned; and staff members will work very hard to maintain comfort, control pain, and maintain the dignity of the patient and his or her family members.
Cancer support groups can be useful adjunctive therapies in the treatment of
cancer patients.[57,58] Recent support group
interventions have demonstrated significant effects on mood disturbance, use of
positive coping strategies, improvement in quality of life, and positive immune
responses.[59-61] Support groups can be found through The Wellness Community,
the American Cancer Society, and many other community resources, including
the social work departments of medical centers or hospitals.
Empirical studies of the efficacy of psychotherapy
Psychotherapy as a treatment for depression in the general adult mental health population has been extensively researched and found to be effective.[62] Recent reviews have also concluded that psychotherapy is an effective intervention for cancer patients experiencing depression.[63,51] In studies designed to prevent the occurrence of depression (i.e., patients not selected because of their depressive symptoms), intervention effects are positive, though small to moderate effect sizes have been reported (effect sizes range from 0.19 to 0.54).[51] However, in those studies in which patients were intentionally selected because they exhibited depressive symptoms, intervention effects were strong (effect size, 0.94).[63] An effect size of 0.94 indicates that the average patient in the treatment group was advantaged, compared with approximately 82% of patients in the control group.
One well-designed randomized clinical trial of a cognitive-behavioral intervention for depressed cancer patients investigated the effect of training in problem solving on symptoms of depression.[64] The intervention consisted of 10 1.5-hour weekly individual psychotherapy sessions focused on training to become an effective problem solver. Problem-solving tasks were emphasized, including skills in (a) better defining and formulating the nature of problems, (b) generating a wide range of alternative solutions, (c) systematically evaluating consequences of a solution while deciding on an optimal one, and (d) evaluating outcome after solution implementation. Between-session homework with tasks relevant to each step was assigned, and patients were provided with a written manual and encouraged to refer to it as problems arose. One hundred thirty-two adult cancer patients were randomly assigned to the problem-solving treatment or a wait-list control. Overall results showed both improved problem-solving abilities and clinically significant decreases in symptoms of depression.
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