Palliative care-Depression
Author:zplhelen | Time: 2009-7-20 21:30:17This is one of my homework during the palliative care traing in Singarpore. Put it here just for memory.
Incidence of major depression and adjustment disorder range from 23% to 60% in adult in-patients with cancer[1].
The causes of depression generally can be divided into two groups: psychosocial factors and physiological factors.
Psychological theories include psychoanalytic approaches (predisposition + loss = depression), interpersonal approaches (disruptions of interpersonal interactions cause depression), and cognitive approached (negative cognition + schemas/ dysfunctional attributional pattern = depression)[2]. Psychosocial factors in elder people are briefly summarized in Picture 1.[3]
Pic. 1 Psychosocial factors contributing to depression in the aged.
Physiological causes include hypercalcemia from bone metastasis, other electrolyte imbalances, deficient vitamin B12 or folate, hypothyroidism or adrenal insufficiency, and paraneoplastic syndromes. Medications are also potential causes: Glucocorticoids such as prednisone and dexamethasone cause alterations in mood, including severe depression. Interferon and interleukin-2 may cause depressive symptoms. Barbiturates, benzodiazepines, and some antibiotics can cause depressive symptoms. Chemotherapeutic agents such as vincristine, vinblastine, procarbazine, and L-asparaginase may induce depression ; whole brain radiation may cause depression as well.[4] Biological theories include genetic approaches and neurobiochemical approaches. Genetic approaches suggest that depression is the result of inheriting genes that predispose to occurrence of depression, but the exact mechanism is not established, maybe by affecting neurotransmission or serotonin-uptake [2,,5]
Hypothalamic–pituitary–adrenal (HPA) axis, the monoaminergic system, the γ-aminobutyric acid (GABA) system, and adult hippocampal neurogenesis may be involved when neurobiochemical approach is concerned in depression.[6]
Studies in animals have shown that exposure to stress can cause alterations in the processes or number of neurons. Repeated stress can cause atrophy of CA3 pyramidal neurons in the hippocampus, including a decrease in the number and length of apical dendrites. Exposure to acute stress decreases the proliferation of cells in the dentate gyrus of the hippocampus. Human brain imaging studies demonstrate that the volume of the hippocampus is decreased in patients with depression or posttraumatic stress disorder, and a decrease in the volume of the subgenual prefrontal cortex and a decrease in the number of neurons and glia are also reported in patients with depression or bipolar disorder. Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, glutamatergic excitoxicity, viral or bacterial infection, excitoxins, hypoxia-ischemia, or vulnerability to stress or other insults as a result of genetic background may result in atrophy and loss of neurons in the hippocampus, as well as cerebral cortex, and thus cause depression.[7]
Depression is reported related to decreased 5-HT level. Synthesis of 5-HT is largely dependent on the availability of its precursor tryptophan (TRP) to the brain. Cytokines, including IL-1, IL-2, IL-6 and IFNs, have been found to reduce TRP availability by activation of the TRP-metabolising enzyme indoleamine-2,3-dioxygenase (IDO). Thus, overstimulation of IDO by cytokines may lead to depletion of serum TRP and subsequent reduction of 5-HT synthesis.[8]
The GABA system is another system related to depression. The neurotransmitter GABA acts on ionotropic GABAA and GABAC receptors as well as metabotropic GABAB receptors. The effective mood stabilizer, valproate, causes an enhancement in the concentration of GABA in the brain, which leads to the postulation that the pathophysiology of mood disorders involved GABAergic deficiency. Neuroimaging studies also suggest the involvement of reduced GABAergic neurotransmission in major depressive disorder. In addition, benzodiazepenes, anxiolytics used in the treatment of depression, directly enhance GABA function by interacting allosterically with the α2 and α5 subunits of the GABAA receptor. [6]
Noradrenergic systems are implicated in depression, too. Norepinephrine is found throughout the brain and it functions as a general regulator of mood and responses to stimuli such as stress. Depression is reported to be associated with a hypofunction of the noradrenergic system, and some antidepressants act by increasing the synaptic availability of norepinephrine. α2-adrenergic and β-adrenergic receptors present in the frontal and prefrontal cortex seem closely related to depression. Studies have shown a down regulation of α2-adrenergic receptors in depression patients. Some antidepressants, such as mirtazapine and robexetine, mediate at least some of their effects through α2-autoreceptors. Norepinephrine transporters responsible for norepinephrine reuptake in the synapse are also a target of antidepressants.[6]
Monoamine theory states that mental depression is due to the deficiency of brain monoaminergic activity. Dopamine is an important monoamine involved. Decrease in dopamine is proposed to be one reason of depression. And this assumption is approved by effective treatment with some dopamine agonists. [9]
A etiologically based, dynamic interactionism model is suggested in a literature to make phathology of depression easier understood.(Picture 2) It is assumed that genetic and early environmental factors interact and lead to relatively stable personality dimensions or cognitive-affective schemas that interacts with life stress, pave the way to depression and other related disorders.[10]
Picture 2. Dynamic interactionism model of depression
Although factors mentioned above have been found to be related to depression, the mechanism is not clear yet.
2.Assessment tool
Primary Care Evaluation of Mental Disorders (PRIME-MD) clinician evaluation guide has been used to assess depression. It is reported to have an overall accuracy of 88% and has been proved validated in oncology settings and palliative settings.[11] The PRIME-MD intends to economically assist a primary care physician in assessing mental disorders. It is a two-stage procedure for consisting of a patient questionnaire (PQ) as an initial screening and a subsequent clinical interview (Clinical Evaluation Guide, CEG). PRIME-MD was proved useful in assessing most of the mental disorders, even in busy primary care settings. [12]
The Hamilton Rating Scale for Depression (HAM-D) is the most widely used rating scale for depression and is considered by many to be the “gold standard”. Many modified versions have been developed to overcome its limited sensitivity to change in depression severity. There is a wide variability in the total number of items included in modified versions, ranging from six item to 31. Several standardized interview questionnaires have been developed to improve the HAM-D's reliability. The most widely used structured interview version is William’s Structured Interview Guide for the HAM-D (SIGH-D).[13]
The Montgomery–Åsberg Depression Rating Scale (MADRS) is a 10-item scale that has overcome the problems in the use of the HAM-D. The 10 MADRS items are chosen from a 65-item comprehensive psychopathology instrument (CPRS) and are to detect changes due to antidepressant treatment and their high correlations with overall change in depression. A limitation of the MADRS is that it does not utilize a standardized interview for ratings, which may lower reliability.[11] A self-assessment version of the MADRS---the MADRS-S has been published.[14]
The Beck Depression Inventory (BDI) is the most often used self-rating instrument for depressive symptoms. The BDI was originally constructed by Beck and co-workers to assess degree of depression in adolescents and adults. Nowadays, the widely used version is a revised one introduced in 1972. The BDI consists of 21 variables with four possible scale steps, rating 0–3. It is possible for patients to chose more than one alternative on each variable, but only the highest rating is counted. BDI reveals three principal factors, reflecting cognitive-affective symptoms and attitudes, impaired performance, and somatic symptoms. However, BDI has been compared with Hamilton Depression Rating Scale (HDRS) and the Montgomery Åsberg Rating Scale (MADRS) in discriminative capacity, respectively. The conclusion was that the two expert rating scales were about equal in this respect, while the performance of the BDI was overall poor.[14]
William W. Eaton, Professor in the Department of Mental Hygiene in the Johns Hopkins University School of Public Health, revised the Center for Epidemiologic Studies of Depression Scale (CESD) into a computer application named CESD-RCESD-R. “Subjects can take either the 20- or 35-item versions with digital audio of the questions. The participant could turn the audio off or on as desired. When the audio is on, the participant can touch any panel on the interface to replay the audio for that text. Headphones with volume control were used to maintain privacy. To facilitate use of the assessment by older persons we used touch screens for test items and response choices. The self-report data can be stored on the local computer or transmitted over the Internet and stored on a server, for instance at a physician's office. The diagnostic and total and sub-scale score results and clinical recommendation are presented to the subjects each time after they complete the questionnaire. This report is printable.”[15] This is my desired assessment tool: it is convenient, both for doctors and patients, quick, reliable, and feasible. And it is reported that the efficiency and reliability of computer assessment are as good as or better than the paper instruments. Even if most patients had not ever used a computer before, they had generally favorable attitudes toward the use of computers, and also reported having a favorable experience with the computer testing system. However, I won’t choose it for my clinical work because the computers would be too expensive for merely assessing depression.
I would like to choose PRIME-MD as it is affordable, simple, accurate, and useful for physicians who are not specialist in psychology.
3.Treatment
Psychosocial treatments
Psychosocial interventions have been proven efficacious in controlled studies, including individual psychotherapy, group psychotherapy, hypnotherapy, multimedia psycho-education, relaxation training and biofeedback, and self-help groups. Some of the studies are randomized controlled studies. These studies showed that appropriate psychosocial treatments could improve quality of life and extend life span of cancer patients as well.[16]
Pharmacological treatments
Only three controlled studies regarding the use of tricyclic antidepressants in cancer patients have been published. All reported positive results, but also reported prominent side effects like sedation.
A literature summarized very well the present and emerging pharmacological treatments as below: [17]
TABLE 1.
Established Antidepressant Treatments
Class Available in United States Level of Support
TCAs Amitriptyline Multiple randomized placebo-controlled trials
Amoxapine
Clomipramine
Desipramine
Doxepin
Imipramine
Nortriptyline
Protriptyline
Trimipramine
MAOIs Isocarboxazid Multiple randomized placebo-controlled trials
Phenelzine
Selegiline (oral)
Tranylcypromine
SSRIs Citalopram Multiple randomized placebo-controlled trials
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
SNRIs Duloxetine Multiple randomized placebo-controlled trials
Venlafaxine
Atypical Bupropion Multiple randomized placebo-controlled trials
Mirtazapine
Nefazodone
Trazodone
ECT Multiple randomized placebo-controlled trials
TABLE 2.
Emerging Antidepressant Treatments: Pharmacotherapy
Class Examples Availability in United States Level of Support/Comments
CRF1 antagonists R121919 No Open data supporting antidepressant effects; liver toxicity precludes use; preclinical data support antidepressant-like and anxiolytic activity (in stressed animals)
CP154,526 No Preclinical data support antidepressant-like and anxiolytic activity (in stressed animals)
Antalarmin No Preclinical data support antidepressant-like and anxiolytic activity (in stressed animals)
DMP-695/696 No Preclinical data support anxiolytic activity (in stressed animals)
CRA1000/CRA1001 No Preclinical data support anxiolytic activity (in stressed animals)
SSR125543A No Preclinical data support antidepressant-like and anxiolytic activity (in stressed animals)
Glucocorticoid receptor (type II) antagonist Mifepristone (RU486) Yes (off label) Open and limited placebo-controlled data support antidepressant and/or antipsychotic activity
NK-1 receptor antagonists MK-869 No Placebo-controlled studies show mixed results (one positive, one negative)
L-759274 No One placebo-controlled study suggests modest antidepressant effects
CP-122721 No Preliminary clinical data suggest antidepressant effects
NMDA antagonists Amantadine Yes (off label) Preliminary data suggest antidepressant effects when used for augmentation
Riluzole (glutamate release inhibitor) Yes (off label) Preliminary data suggest antidepressant effects in bipolar patients; no data in MDD
Transdermal MAOIs Selegiline patch Yes (off label) Placebo-controlled studies show mixed results
Triple reuptake inhibitors DOV 21,947 No Preclinical data support antidepressant-like effects
DOV 216,303 No Preclinical data support antidepressant-like effects; preliminary data support safety in humans
Atypical antipsychotic augmentation Multiple Yes (off label) Multiple open and small placebo-controlled studies support antidepressant effects
TABLE 3.
Emerging Antidepressant Treatments: Focal Brain Stimulation
Type of Stimulation Availability in United States Level of Support/Comments
VNS Yes Placebo-controlled data negative; however, long-term open data support antidepressant effects in severely refractory patients
TMS No Multiple small placebo-controlled studies support at least modest antidepressant effects; large, multi-center studies are ongoing
MST No Preliminary clinical data support potential antidepressant effects
DBS Yes (off label) One small open study supports antidepressant effects
TMS = transcranial magnetic stimulation.
References:
1. D. Jeffrey Newport and Charles B. Nemeroff. Assessment and treatment of depression in the cancer patient. Journal of Psychosomatic Research, Volume 45, Issue 3, September 1998, Pages 215-237
2. Rick E. Ingram and Christine Scher. Depression.The Disorders, 2001, Pages 177-186
3. George S. Alexopoulos, Kathleen Buckwalter, Jason Olin, Rick Martinez, Cynthia Wainscott and K. Ranga R. Krishnan. Comorbidity of late life depression: an opportunity for research on mechanisms and treatment. Biological Psychiatry, Volume 52, Issue 6, 15 September 2002, Pages 543-558
4. Andrew J.Roth and Reena Modi. Psychiatric issues in older cancer patients. Critical Reviews in Oncology/Hematology Volume 48, Issue 2, November 2003, Pages 185-197
5. Richard J. Wurtman. Genes, stress, and depression. Metabolism, Volume 54, Issue 5, Supplement 1, May 2005, Pages 16-19
6. Chirisse Taylor, Ashwana D. Fricker, Lakshmi A. Devi and Ivone Gomes. Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways. Cellular Signalling, Volume 17, Issue 5, May 2005, Pages 549-557
7. R. S. Duman. Pathophysiology of depression: the concept of synaptic plasticity. European Psychiatry, Volume 17, Supplement 3, July 2002, Pages 306-310
8. Olga J.G. Schiepers, Marieke C. Wichers and Michael Maes. Cytokines and major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 29, Issue 2, February 2005, Pages 201-217
9. Abdalla Salem Elhwuegi. Central monoamines and their role in major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 28, Issue 3, May 2004, Pages 435-451
10. Patrick Luyten, Sidney J. Blatt, Boudewijn Van Houdenhove and Jozef Corveleyn. Depression research and treatment: Are we skating to where the puck is going to be?Clinical Psychology Review, Volume 26, Issue 8, December 2006, Pages 985-999
11. Keith G. Wilson, Harvey Max Chochinov, Merika Graham Skirko MSW, et al. Depression and Anxiety Disorders in Palliative Cancer Care. Journal of Pain and Symptom Management Volume 33, Issue 2, February 2007, Pages 118-129
12. Bernd Loerch, Armin Szegedi, Ralf Kohnen and Otto Benkert. The Primary Care Evaluation of Mental Disorders (PRIME-MD), German version: a comparison with the CIDI.Journal of Psychiatric Research, Volume 34, Issue 3, 1 May 2000, Pages 211-220
13. Rebecca W. Iannuzzo, Judith Jaeger, Joseph F. Goldberg, Vivian Kafantaris and M. Elizabeth Sublette. Development and reliability of the HAM-D/MADRS Interview: An integrated depression symptom rating scale. Psychiatry Research, Volume 145, Issue 1, 29 November 2006, Pages 21-37
14. Pär Svanborg and Marie Åsberg. A comparison between the Beck Depression Inventory (BDI) and the self-rating version of the Montgomery Åsberg Depression Rating Scale (MADRS). Journal of Affective Disorders, Volume 64, Issues 2-3, May 2001, Pages 203-216
15. Reyis Kurt, Hillary R. Bogner, Joseph B. Straton, Allen Y. Tien and Joseph J. Gallo. Computer-assisted assessment of depression and function in older primary care patients. Computer Methods and Programs in Biomedicine, Volume 73, Issue 2, February 2004, Pages 165-171
16. D. Jeffrey Newport and Charles B. Nemeroff. Assessment and treatment of depression in the cancer patient. Journal of Psychosomatic Research, Volume 45, Issue 3, September 1998, Pages 215-237
17. Paul E. Holtzheimer III and Charles B. Nemeroff. Advances in the Treatment of Depression.NeuroRX, Volume 3, Issue 1, January 2006, Pages 42-56
Pathophysiology and causes of depression
Incidence of major depression and adjustment disorder range from 23% to 60% in adult in-patients with cancer[1].
The causes of depression generally can be divided into two groups: psychosocial factors and physiological factors.
Psychological theories include psychoanalytic approaches (predisposition + loss = depression), interpersonal approaches (disruptions of interpersonal interactions cause depression), and cognitive approached (negative cognition + schemas/ dysfunctional attributional pattern = depression)[2]. Psychosocial factors in elder people are briefly summarized in Picture 1.[3]
Pic. 1 Psychosocial factors contributing to depression in the aged.
Physiological causes include hypercalcemia from bone metastasis, other electrolyte imbalances, deficient vitamin B12 or folate, hypothyroidism or adrenal insufficiency, and paraneoplastic syndromes. Medications are also potential causes: Glucocorticoids such as prednisone and dexamethasone cause alterations in mood, including severe depression. Interferon and interleukin-2 may cause depressive symptoms. Barbiturates, benzodiazepines, and some antibiotics can cause depressive symptoms. Chemotherapeutic agents such as vincristine, vinblastine, procarbazine, and L-asparaginase may induce depression ; whole brain radiation may cause depression as well.[4] Biological theories include genetic approaches and neurobiochemical approaches. Genetic approaches suggest that depression is the result of inheriting genes that predispose to occurrence of depression, but the exact mechanism is not established, maybe by affecting neurotransmission or serotonin-uptake [2,,5]
Hypothalamic–pituitary–adrenal (HPA) axis, the monoaminergic system, the γ-aminobutyric acid (GABA) system, and adult hippocampal neurogenesis may be involved when neurobiochemical approach is concerned in depression.[6]
Studies in animals have shown that exposure to stress can cause alterations in the processes or number of neurons. Repeated stress can cause atrophy of CA3 pyramidal neurons in the hippocampus, including a decrease in the number and length of apical dendrites. Exposure to acute stress decreases the proliferation of cells in the dentate gyrus of the hippocampus. Human brain imaging studies demonstrate that the volume of the hippocampus is decreased in patients with depression or posttraumatic stress disorder, and a decrease in the volume of the subgenual prefrontal cortex and a decrease in the number of neurons and glia are also reported in patients with depression or bipolar disorder. Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, glutamatergic excitoxicity, viral or bacterial infection, excitoxins, hypoxia-ischemia, or vulnerability to stress or other insults as a result of genetic background may result in atrophy and loss of neurons in the hippocampus, as well as cerebral cortex, and thus cause depression.[7]
Depression is reported related to decreased 5-HT level. Synthesis of 5-HT is largely dependent on the availability of its precursor tryptophan (TRP) to the brain. Cytokines, including IL-1, IL-2, IL-6 and IFNs, have been found to reduce TRP availability by activation of the TRP-metabolising enzyme indoleamine-2,3-dioxygenase (IDO). Thus, overstimulation of IDO by cytokines may lead to depletion of serum TRP and subsequent reduction of 5-HT synthesis.[8]
The GABA system is another system related to depression. The neurotransmitter GABA acts on ionotropic GABAA and GABAC receptors as well as metabotropic GABAB receptors. The effective mood stabilizer, valproate, causes an enhancement in the concentration of GABA in the brain, which leads to the postulation that the pathophysiology of mood disorders involved GABAergic deficiency. Neuroimaging studies also suggest the involvement of reduced GABAergic neurotransmission in major depressive disorder. In addition, benzodiazepenes, anxiolytics used in the treatment of depression, directly enhance GABA function by interacting allosterically with the α2 and α5 subunits of the GABAA receptor. [6]
Noradrenergic systems are implicated in depression, too. Norepinephrine is found throughout the brain and it functions as a general regulator of mood and responses to stimuli such as stress. Depression is reported to be associated with a hypofunction of the noradrenergic system, and some antidepressants act by increasing the synaptic availability of norepinephrine. α2-adrenergic and β-adrenergic receptors present in the frontal and prefrontal cortex seem closely related to depression. Studies have shown a down regulation of α2-adrenergic receptors in depression patients. Some antidepressants, such as mirtazapine and robexetine, mediate at least some of their effects through α2-autoreceptors. Norepinephrine transporters responsible for norepinephrine reuptake in the synapse are also a target of antidepressants.[6]
Monoamine theory states that mental depression is due to the deficiency of brain monoaminergic activity. Dopamine is an important monoamine involved. Decrease in dopamine is proposed to be one reason of depression. And this assumption is approved by effective treatment with some dopamine agonists. [9]
A etiologically based, dynamic interactionism model is suggested in a literature to make phathology of depression easier understood.(Picture 2) It is assumed that genetic and early environmental factors interact and lead to relatively stable personality dimensions or cognitive-affective schemas that interacts with life stress, pave the way to depression and other related disorders.[10]
Picture 2. Dynamic interactionism model of depression
Although factors mentioned above have been found to be related to depression, the mechanism is not clear yet.
2.Assessment tool
Primary Care Evaluation of Mental Disorders (PRIME-MD) clinician evaluation guide has been used to assess depression. It is reported to have an overall accuracy of 88% and has been proved validated in oncology settings and palliative settings.[11] The PRIME-MD intends to economically assist a primary care physician in assessing mental disorders. It is a two-stage procedure for consisting of a patient questionnaire (PQ) as an initial screening and a subsequent clinical interview (Clinical Evaluation Guide, CEG). PRIME-MD was proved useful in assessing most of the mental disorders, even in busy primary care settings. [12]
The Hamilton Rating Scale for Depression (HAM-D) is the most widely used rating scale for depression and is considered by many to be the “gold standard”. Many modified versions have been developed to overcome its limited sensitivity to change in depression severity. There is a wide variability in the total number of items included in modified versions, ranging from six item to 31. Several standardized interview questionnaires have been developed to improve the HAM-D's reliability. The most widely used structured interview version is William’s Structured Interview Guide for the HAM-D (SIGH-D).[13]
The Montgomery–Åsberg Depression Rating Scale (MADRS) is a 10-item scale that has overcome the problems in the use of the HAM-D. The 10 MADRS items are chosen from a 65-item comprehensive psychopathology instrument (CPRS) and are to detect changes due to antidepressant treatment and their high correlations with overall change in depression. A limitation of the MADRS is that it does not utilize a standardized interview for ratings, which may lower reliability.[11] A self-assessment version of the MADRS---the MADRS-S has been published.[14]
The Beck Depression Inventory (BDI) is the most often used self-rating instrument for depressive symptoms. The BDI was originally constructed by Beck and co-workers to assess degree of depression in adolescents and adults. Nowadays, the widely used version is a revised one introduced in 1972. The BDI consists of 21 variables with four possible scale steps, rating 0–3. It is possible for patients to chose more than one alternative on each variable, but only the highest rating is counted. BDI reveals three principal factors, reflecting cognitive-affective symptoms and attitudes, impaired performance, and somatic symptoms. However, BDI has been compared with Hamilton Depression Rating Scale (HDRS) and the Montgomery Åsberg Rating Scale (MADRS) in discriminative capacity, respectively. The conclusion was that the two expert rating scales were about equal in this respect, while the performance of the BDI was overall poor.[14]
William W. Eaton, Professor in the Department of Mental Hygiene in the Johns Hopkins University School of Public Health, revised the Center for Epidemiologic Studies of Depression Scale (CESD) into a computer application named CESD-RCESD-R. “Subjects can take either the 20- or 35-item versions with digital audio of the questions. The participant could turn the audio off or on as desired. When the audio is on, the participant can touch any panel on the interface to replay the audio for that text. Headphones with volume control were used to maintain privacy. To facilitate use of the assessment by older persons we used touch screens for test items and response choices. The self-report data can be stored on the local computer or transmitted over the Internet and stored on a server, for instance at a physician's office. The diagnostic and total and sub-scale score results and clinical recommendation are presented to the subjects each time after they complete the questionnaire. This report is printable.”[15] This is my desired assessment tool: it is convenient, both for doctors and patients, quick, reliable, and feasible. And it is reported that the efficiency and reliability of computer assessment are as good as or better than the paper instruments. Even if most patients had not ever used a computer before, they had generally favorable attitudes toward the use of computers, and also reported having a favorable experience with the computer testing system. However, I won’t choose it for my clinical work because the computers would be too expensive for merely assessing depression.
I would like to choose PRIME-MD as it is affordable, simple, accurate, and useful for physicians who are not specialist in psychology.
3.Treatment
Psychosocial treatments
Psychosocial interventions have been proven efficacious in controlled studies, including individual psychotherapy, group psychotherapy, hypnotherapy, multimedia psycho-education, relaxation training and biofeedback, and self-help groups. Some of the studies are randomized controlled studies. These studies showed that appropriate psychosocial treatments could improve quality of life and extend life span of cancer patients as well.[16]
Pharmacological treatments
Only three controlled studies regarding the use of tricyclic antidepressants in cancer patients have been published. All reported positive results, but also reported prominent side effects like sedation.
A literature summarized very well the present and emerging pharmacological treatments as below: [17]
TABLE 1.
Established Antidepressant Treatments
Class Available in United States Level of Support
TCAs Amitriptyline Multiple randomized placebo-controlled trials
Amoxapine
Clomipramine
Desipramine
Doxepin
Imipramine
Nortriptyline
Protriptyline
Trimipramine
MAOIs Isocarboxazid Multiple randomized placebo-controlled trials
Phenelzine
Selegiline (oral)
Tranylcypromine
SSRIs Citalopram Multiple randomized placebo-controlled trials
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
SNRIs Duloxetine Multiple randomized placebo-controlled trials
Venlafaxine
Atypical Bupropion Multiple randomized placebo-controlled trials
Mirtazapine
Nefazodone
Trazodone
ECT Multiple randomized placebo-controlled trials
TABLE 2.
Emerging Antidepressant Treatments: Pharmacotherapy
Class Examples Availability in United States Level of Support/Comments
CRF1 antagonists R121919 No Open data supporting antidepressant effects; liver toxicity precludes use; preclinical data support antidepressant-like and anxiolytic activity (in stressed animals)
CP154,526 No Preclinical data support antidepressant-like and anxiolytic activity (in stressed animals)
Antalarmin No Preclinical data support antidepressant-like and anxiolytic activity (in stressed animals)
DMP-695/696 No Preclinical data support anxiolytic activity (in stressed animals)
CRA1000/CRA1001 No Preclinical data support anxiolytic activity (in stressed animals)
SSR125543A No Preclinical data support antidepressant-like and anxiolytic activity (in stressed animals)
Glucocorticoid receptor (type II) antagonist Mifepristone (RU486) Yes (off label) Open and limited placebo-controlled data support antidepressant and/or antipsychotic activity
NK-1 receptor antagonists MK-869 No Placebo-controlled studies show mixed results (one positive, one negative)
L-759274 No One placebo-controlled study suggests modest antidepressant effects
CP-122721 No Preliminary clinical data suggest antidepressant effects
NMDA antagonists Amantadine Yes (off label) Preliminary data suggest antidepressant effects when used for augmentation
Riluzole (glutamate release inhibitor) Yes (off label) Preliminary data suggest antidepressant effects in bipolar patients; no data in MDD
Transdermal MAOIs Selegiline patch Yes (off label) Placebo-controlled studies show mixed results
Triple reuptake inhibitors DOV 21,947 No Preclinical data support antidepressant-like effects
DOV 216,303 No Preclinical data support antidepressant-like effects; preliminary data support safety in humans
Atypical antipsychotic augmentation Multiple Yes (off label) Multiple open and small placebo-controlled studies support antidepressant effects
TABLE 3.
Emerging Antidepressant Treatments: Focal Brain Stimulation
Type of Stimulation Availability in United States Level of Support/Comments
VNS Yes Placebo-controlled data negative; however, long-term open data support antidepressant effects in severely refractory patients
TMS No Multiple small placebo-controlled studies support at least modest antidepressant effects; large, multi-center studies are ongoing
MST No Preliminary clinical data support potential antidepressant effects
DBS Yes (off label) One small open study supports antidepressant effects
TMS = transcranial magnetic stimulation.
References:
1. D. Jeffrey Newport and Charles B. Nemeroff. Assessment and treatment of depression in the cancer patient. Journal of Psychosomatic Research, Volume 45, Issue 3, September 1998, Pages 215-237
2. Rick E. Ingram and Christine Scher. Depression.The Disorders, 2001, Pages 177-186
3. George S. Alexopoulos, Kathleen Buckwalter, Jason Olin, Rick Martinez, Cynthia Wainscott and K. Ranga R. Krishnan. Comorbidity of late life depression: an opportunity for research on mechanisms and treatment. Biological Psychiatry, Volume 52, Issue 6, 15 September 2002, Pages 543-558
4. Andrew J.Roth and Reena Modi. Psychiatric issues in older cancer patients. Critical Reviews in Oncology/Hematology Volume 48, Issue 2, November 2003, Pages 185-197
5. Richard J. Wurtman. Genes, stress, and depression. Metabolism, Volume 54, Issue 5, Supplement 1, May 2005, Pages 16-19
6. Chirisse Taylor, Ashwana D. Fricker, Lakshmi A. Devi and Ivone Gomes. Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways. Cellular Signalling, Volume 17, Issue 5, May 2005, Pages 549-557
7. R. S. Duman. Pathophysiology of depression: the concept of synaptic plasticity. European Psychiatry, Volume 17, Supplement 3, July 2002, Pages 306-310
8. Olga J.G. Schiepers, Marieke C. Wichers and Michael Maes. Cytokines and major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 29, Issue 2, February 2005, Pages 201-217
9. Abdalla Salem Elhwuegi. Central monoamines and their role in major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 28, Issue 3, May 2004, Pages 435-451
10. Patrick Luyten, Sidney J. Blatt, Boudewijn Van Houdenhove and Jozef Corveleyn. Depression research and treatment: Are we skating to where the puck is going to be?Clinical Psychology Review, Volume 26, Issue 8, December 2006, Pages 985-999
11. Keith G. Wilson, Harvey Max Chochinov, Merika Graham Skirko MSW, et al. Depression and Anxiety Disorders in Palliative Cancer Care. Journal of Pain and Symptom Management Volume 33, Issue 2, February 2007, Pages 118-129
12. Bernd Loerch, Armin Szegedi, Ralf Kohnen and Otto Benkert. The Primary Care Evaluation of Mental Disorders (PRIME-MD), German version: a comparison with the CIDI.Journal of Psychiatric Research, Volume 34, Issue 3, 1 May 2000, Pages 211-220
13. Rebecca W. Iannuzzo, Judith Jaeger, Joseph F. Goldberg, Vivian Kafantaris and M. Elizabeth Sublette. Development and reliability of the HAM-D/MADRS Interview: An integrated depression symptom rating scale. Psychiatry Research, Volume 145, Issue 1, 29 November 2006, Pages 21-37
14. Pär Svanborg and Marie Åsberg. A comparison between the Beck Depression Inventory (BDI) and the self-rating version of the Montgomery Åsberg Depression Rating Scale (MADRS). Journal of Affective Disorders, Volume 64, Issues 2-3, May 2001, Pages 203-216
15. Reyis Kurt, Hillary R. Bogner, Joseph B. Straton, Allen Y. Tien and Joseph J. Gallo. Computer-assisted assessment of depression and function in older primary care patients. Computer Methods and Programs in Biomedicine, Volume 73, Issue 2, February 2004, Pages 165-171
16. D. Jeffrey Newport and Charles B. Nemeroff. Assessment and treatment of depression in the cancer patient. Journal of Psychosomatic Research, Volume 45, Issue 3, September 1998, Pages 215-237
17. Paul E. Holtzheimer III and Charles B. Nemeroff. Advances in the Treatment of Depression.NeuroRX, Volume 3, Issue 1, January 2006, Pages 42-56
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