secondary depression: etiopathogenesis & management
DESCRIPTION
ppt on secondary depressionTRANSCRIPT
Secondary DepressionEtiopathogenesis &
management
Presenter:
Dr Angshuman Kalita
Chairperson:
Dr Utpal BoraAsst Professor
Deptt of PsychiatryDate: 03/09/2014
Secondary depression is a depression in an
individual who has one or more pre-existing,
nonaffective psychiatric disorders or an
incapacitating or life-threatening medical
illness which precedes and parallels the
symptoms of depression.
Journal of Affective Disorders.1981; 3 : 25-35
Primary vs. secondary depression
In secondary, depression emerges after the medical illness. In primary, the depressive situation is already established, with the medical illness superimposed upon it
Secondary Depression
• For every 5 patients who are seen with a diagnosis of depression, approximately 2 should be classified as secondary
• The symptom picture of secondary depression is almost indistinguishable from primary depression
MDD is estimated to occur in 4% of those with 1 or more medical conditions compared with 2.8% of those without.
Medical illnesses may exacerbate or cause depressive signs or symptoms through effect on mood, neuroendocrine & immune funtion, self-care abilities & social interaction which are mediated through the patient’s premorbid personality, ego defences & coping style
Inflammation as a cause of depression
• Depression has been linked with activation of CMI since the early 1990s linking together the observations of increased HPA axis activation & increased inflammatory response in depression.
• In recent studies IL 1a levels were found to significantly predict the development of depressive symptoms at 3 & 6 year follow up suggesting a causal role of inflammation in development of late life depression
• Several studies have found increased IL-6 levels to be a strong predictor of depression. The observation of a relationship between hippocampal atrophy & high levels of IL-6 suggest an inflammatory mechanism for hippocampal volume loss in depression
• Several studies have suggested that depressed patients have shorter telomeres than age matched controls suggesting a relationship between depression & more rapid cellular aging
Schizophrenia and depression
Features of SchizophreniaPositive symptoms- Delusions- Hallucinations- Disorganization
Cognitive deficits
Functional ImpairmentsWork
Interpersonal relationshipsSelf-care
Negative symptoms- emotional range- expression of emotion- motivation/drive- interests- social drive - poverty of speech
Mood symptomsDisorganization- speech- behavior
Depressive Symptoms– Primary to schizophrenia
– “Reactive”• psychosis is frightening• reality of illness is demoralizing
– Co-morbid disorder• major depressive episode
• Disturbance of consciousness caused by head trauma, encephalitis, or other central nervous system disorders may lead to depression which can for several weeks or months.
• Symptom Patterns Depressive mood combined with amnestic symptoms Marked anxiety and delusion Irritability and impaired social functioning Excessive or inappropriate guilt under depressive mood Hallucination and delusion
1. Depression in the recovery stage from disturbance of consciousness
JMAJ.2001; 44 : 279–282
(a.) Depression in cerebrovascular disorder• In chronic cerebral vascular insufficiency,
affective symptoms such as affective incontinence, depression, impatience, irritability, and affective flattening may occur
2. Depression in Neurological Disease
JMAJ.2001; 44 : 279–282
• Studies on depression secondary to focal brain lesions have indicated that frontal lobe damage, especially in the dominant hemisphere, is associated with an increased likelihood of developing depression.
• Robinson et al demonstrated that depression was likely to occur after a stroke affecting the left hemisphere, especially in the left frontal area.
• Among the frontal regions, the prefrontal and paralimbic frontal areas, especially on the left side, have been repeatedly pointed out to be the most crucial sites.
• Baxter et al demonstrated that depressive patients (unipolar depression and bipolar depression) had a glucose hypometabolism in the bilateral anterolateral prefrontal cortices and that the severity of depression correlated with a decrease in glucose metabolic rate & decrease in blood flow in both areas
(b.) Depression in Alzheimer’s disease
• It is frequent for affective symptoms such as
depressive mood, decreased spontaneity, affective
lability, affective flattening, and anxiety/impatience to
occur as prodromal symptoms of dementia in the early
stage of Alzheimer’s disease.
• In these cases, anxiety, depressive mood, behavioural
retardation, and inactivity are common, whereas
feelings of guilt, suicidal ideation, and secondary
delusion are rare.
2. Depression in Neurological Disease
JMAJ.2001; 44 : 279–282
Depression and Parkinson’s Disease
• Depression may occur at any time during the course of PD and may occur even before the motor features.
• Depression occurs in 40 to 50% of persons with PD at some time in their illness, 5-20% moderate to severe
DEPRESSION INPARKINSON’S DISEASE
•Characterized by: Feeling of guilt Lack of self esteem Loss of initiative Helplessness, remorse, sadness
• Associated with increased disability
• Associated with impaired quality of life.
• Tends to be under recognized and under treated in patients with PD– As many as 40% of depressed patients are not treated or not referred for treatment
Depression in PD: how common is it and what are the outcomes
WHY ???
• Major depression and Parkinson’s disease share common symptoms.
• Depression may be confused with other conditions such as dementia and apathy.
• Patients may be hesitant to bring up depressive symptoms to their doctor.
Why is Depression in PD under recognized?
• Compared to non-PD depressed patients:
– More:• anguish, anxiety, irritability,• pessimism regarding the future, • suicidal ideation
– Less:• guilt, self blame, • feelings of failure, • suicide• Low incidence of delusion & hallucination•Lack of diurnal variation
Depression in PD: symptoms
cause of depression in PD is unknown
The loss of mesocortical & mesolimbic dopamine connections to the frontal lobe & disruption of monoaminergic afferent from the mesencephalon has been implicated in pathogenesis of depression in PD on the basis of reduced brain serotonin, nigral & ventral tegmental area dopamine & locus ceruleus norepinephrine in patients who die from PD
Loss of these brainstem monoaminergic neurons, with degeration of their respective cortical & subcortical projection, is a plausible mechanism of depression in this patients
What causes depression in PD?
(d.) Depression in other neurologic diseases
Following neurodegenerative diseases may be
complicated by depression:
• Huntington’s disease
• Progressive supranuclear palsy,
• Fronto-temporal lobe dementia
• Neurosyphilis, toxic diseases,
• pellagra, folic acid deficiency, and Wernicke’s
encephalopathy
2. Depression in Neurological Disease
JMAJ.2001; 44 : 279–282
Depression as a symptom of dementia
• Depression has been noted to occur in patients with a previously diagnosed dementia or MCI suggesting that depression could be considered one of the many “ behavioral & psychological symptoms of dementia”(BPSD). Depressive symptoms in patients with dementia have been linked with frontal & parietal white matter hyper intensities
Depression after traumatic brain injury
Depressive disorders are the most common neuropsychiatric sequels of traumatic brain injury
Cases in which depressive disorder develop in the late post injury period , psychological & social factors appears to be etiologically important
Depression in medically ill patients
• Depression in medically ill patients is first & foremost a phenotype. Many underlying etiologies may take a final common pathway of producing such a phenotype, but have divergent implications for prognosis and management. Thus appropriate management requires first establishing the most likely diagnosis that has caused depression
Respiratorydisorders
DEPRESSION DUE TO
Estimated 10 – 42% COPD patients suffer from comorbid depression
Increases with the severity of COPD
Respirology. 2012; 17: 627-38
Patients with severe COPD have a 2.5 times greater risk of developing depression
• Highest rate of depression is seen those who are oxygen dependant
Etiopathogenesis
Loss of independenceInability to carry out previous activities, Social isolation may play a role in the
depression these patients experiences
Many patients have temporary depressive symptoms during COPD-related exacerbations that resolve once their respiratory symptoms improve
• Awareness of the effects that medications used for depression & COPD have on each illness must be maintained. – Corticosteroid used in the treatment of
COPD may cause depressive symptoms. – Oral theophyllines, may disrupt sleep in
depressed patients with COPD
Overlapping symptoms
• Decreased appetite• Sleep disturbances• Lack of energy• Poor memory & concentration• Weight loss• Lack of confidence• Feelings of hopelessness
It is difficult to decide when these symptoms are
secondary to depression and when they are secondary to
COPD Respirology. 2012; 17: 627-38
• As symptoms of depression & COPD may overlap, care must be taken to avoid mistaking symptoms of worsening COPD for depression & vice versa, but sustained depressed mood or anhedonia should not be attributed to lung disease alone
Cognitive behavioral therapy• Low intensity intervention for mild to
moderate depression• High intensity intervention in combination
with medication for moderate to severe depression
Pulmonary Rehabilitation:• Evidence confirms reduction of depressive
symptoms with this therapy Pharmacological treatment• Despite the lack of rigorous evidence,
pharmacological therapy is the most common treatment of depression in COPD
Respirology. 2012; 17: 627-38
Venlafaxine or mirtazapine are useful for patients who are non responsive to SSRI
SSRIs
considered the first-line agents
for control of depression
symptoms in patients with
COPD
Respirology. 2012; 17: 627-38
Weight gain was a side-effect with long term use of ADs.
It may be of particular benefit in patients with severe COPD, low BMI and poor prognosis
Cardiovascular disorders
DEPRESSION DUE TO
DepressionHeart disease
• Depressed individuals are more likely to have conventional cardiac risk factors:– Hypertension, high cholesterol, diabetes,
obesity– Maladaptive health behaviours like smoking,
unhealthy diet, physical inactivity and medical non-adherence
• Heart disease can also precipitate depression:– Post-MI, Acute Coronary Syndrome,
Congestive Heart FailureCurr Psychiatry Rep. 2010; 12: 255-64
• Since the 1970s,studies have delineated a link between depression & Cardiovascular disease and mortality.
• Studies also indicate that 16%-18% of patients after an acute MI are affected by MDD. A total of one third will experience depression during the 1st year, especially in first 6 months
• An estimated 15%-23% of those with established IHD may have MDD & depression in this population conveys a three to four fold increase in subsequent CVS morbidity & mortality
• The Rotterdam study found that subjects age 60 years & older with atherosclerosis correlated with higher depression rating scores
• The past decade has provided increasing evidence for a “vascular depression”. It has also been described as a depression–executive dysfunction syndrome
• Characterized by – psychomotor retardation, – greater anhedonia,– impaired verbal fluency & visual naming &– poor performance on task of initiation &
perseveration
• It is associated with less family history, greater functional disability & perhaps worse treatment outcomes
Behavioural mechanisms linking depression and heart disease - I
Mechanism Comment Effect on heart disease
Sleep disturbance Common in depression; may be exacerbated by heart disease symptoms
Leads to autonomic hyperactivity which is linked to obesity, diabetes, hypertension, and the metabolic syndrome
Physical inactivity Common in depression Increases cardiovascular morbidity and mortality
Cigarette smoking Individuals with depression are more likely to smoke, and depressed smokers are less likely to quit
Increases cardiovascular morbidity and mortality
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Behavioral mechanisms linking depression and heart disease - I
Mechanism Comment Effect on heart disease
Poor hygiene Inattentiveness to self care is more common in depression; depression is associated with decreased salivary flow and cariogenic diet.
Periodontal disease (especially gingivitis) has been associated with increased cardiovascular morbidity and mortality
Adherence to treatment Patients with depression are less likely to adhere to medical therapy and risk reducing behaviors
Poor adherence to medical therapy is associated with increased cardiovascular morbidity and mortality
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Psychological mechanisms linking depression and heart disease - II
Mechanism Comment Effect on heart disease
Attitudes about treatment Depression may be associated with negative attitudes toward treatment. Individuals with depression may perceive more, and have greater concern about, medication side effects
Attitudes about treatment appear important to therapeutic effect; even poor adherers to placebo in cardiovascular disease trials have increased mortality
Social isolation Depression is associated with less social support and greater social isolation
Decreased social support and social isolation are associated with increased cardiovascular morbidity and mortality
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Psychological mechanisms linking depression and heart disease - II
Mechanism Comment Effect on heart disease
Cardiovascular stress response Some studies show that depression is associated with heightened, and some with attenuated, cardiovascular reactivity to physiological stress
Autonomic hyperactivity at baseline and in response to stressors may increase cardiovascular risk
Self-efficacy Depression is often associated with low self-efficacy
Low self-efficacy is associated with greater symptom burden and physical limitation; worse quality of life; poor adherence; and possibly increased cardiovascular morbidity and mortality
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Biological mechanisms possibly underlying the association between depression and heart disease
• Autonomic nervous system dysregulation (low heart rate variability is a powerful predictor of mortality in patients with coronary heart disease; depressed patients have a decreased heart rate variability than non-depressed controls).
• Blood clotting and endothelial dysfunction (depression is associated with enhanced platelet activation, increased plasma levels of pro-thrombogenic factors and reduced endothelial dependent vasodilatation).
• Inflammation
• Neuroendocrine abnormalities (depression is associated with an increased activity of the hypothalamic-pituitary-adrenal axis, with a consequent overstimulation of the sympathetic nervous system).
From Monteleone P. The association between depression and heart disease: the role of biological mechanisms. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
• Exact etiopathogenesis remains unclear
• Vascular disease may contribute to depression by affecting sub cortical structures involved in mood regulation & the white matter pathways that connect these structures to the frontal cortex
• Increased activity by 5-lipoxygenase has been proposed as a common mechanism for atherosclerosis & depression
Role of genetic factors in explaining the association between depression and heart
disease
• Twin and family studies provide evidence for a role of genetic pleiotropy in the association between major depression and coronary heart disease (i.e., genetic variants influence risk factors that independently increase the risk for both major depression and coronary heart disease). The actual genetic variants at the base of this pleiotropy remain to be detected.
From de Geus E. The association between depression and heart disease: the role of genetic factors. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Antidepressants in post-myocardial (MI) infarction
• (SSRIs) are safe in the immediate post-MI period and are effective antidepressants.
• There is strong suggestion that antidepressants in general, and SSRIs in particular, reduce morbidity and mortality in post-MI depressed patients.
From Glassman AH, Bigger JT. Depression and cardiovascular disease: the safety of antidepressant drugs and their ability to improve mood and reduce medical morbidity. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Recognition and management of depression in post-myocardial infarction (MI) patients
• Post-MI patients should be screened for the presence of depression by a simple well-validated instrument
• When a patient screens positive for depression, a primary care provider familiar with managing depression should follow and support him/her, with the regular supervision by a psychiatrist.
From Glassman AH, Bigger JT. Depression and cardiovascular disease: the safety of antidepressant drugs and their ability to improve mood and reduce medical morbidity. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Recommendations for clinicians providing care for patients with comorbid depression and heart
disease - I
• Sleep. Ask your patients about their sleep habits.
• Physical activity. Strongly encourage your patients to exercise at home and to become involved (and stay involved) in structured exercise programs.
• Cigarette smoking. Ask every patient whether he/she smokes, and counsel about smoking cessation if appropriate.
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Recommendations for clinicians providing care for patients with comorbid depression and heart
disease - II• Medication adherence. Specifically address the issue of medication adherence
with every patient and try to decrease barriers to adherence.
• Attitudes and beliefs about cardiac treatment regimens. Discuss the importance of each medication, what the goals of treatment are, and how the patient’s particular health goals are more likely to be achieved by adhering to a particular medical treatment.
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
Recommendations for clinicians providing care for patients with comorbid depression and heart
disease - III• Social isolation. Encourage patients to socialize with family and friends,
encourage the patient to participate in group activities that may be appropriate and desirable
• Self-efficacy. If the patient’s confidence is low, consider specific counseling that might enhance self-efficacy.
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.
HYPERTENSION
• SNRIs increase BP mildly. it is because of Drug-drug interactions between antihypertensive medications and ADs
Hypertension induced due to treatment with SNRI may respond by lowering the dose.
DIABETES
DEPRESSION DUE TO
Prevalence of comorbidity
In a review including 21,351 adults, it was found that the prevalence of MDD in people with diabetes was
11% and the prevalence of clinically relevant depression was 31%.
- A meta-analysis of 42 published studies
An Indian study, published in 2010, found that 23% diabetics met the
criteria for major depression
Diabetes Research and Clinical Practice. 2010; 87: 302-312Indian J Med Res. 2010; 132: 195-200
Effect of Depression on Glycemic control
Depression was significantly associated with poor glycemic control in individuals with type 1 and type 2
diabetes- A meta-analysis of 24 studies
Another study found that over 4 years of follow-up, depression was
significantly associated with persistently higher HbA1c levels over
the period, bearing a longitudinal relationship.
Diabetes Research and Clinical Practice. 2010; 87: 302-312
Effect of Depression on Glycemic controlSelf-Care
Negative impact on patient initiated activities such as:
• less physical activity,
• unhealthy diet, and
• lower adherence to oral medications
Diabetes Research and Clinical Practice. 2010; 87: 302-312
Effect of Depression on Self-CareMortality
Effect of depression on all-cause mortality in patients
with diabetes
Coexistence of diabetes and depression is
associated with significantly higher
risk of death.This risk is beyond that due to having either diabetes or depression alone
Diabetes Research and Clinical Practice. 2010; 87: 302-312
Diabetes Research and Clinical Practice. 2010; 87: 302-312
Effect of Depression on
Diabetes complication
sA meta-analysis of 27 studies found
that comorbid depression in diabetics leads to significantly greater diabetes
complications like:Diabetic retinopathy
NephropathyNeuropathy
Microvascular complicationsSexual dysfunctions
DIABETES• Strict monitoring of blood glucose
is required
• Use of TCAs may be associated with worsened glycemic control
SSRIs preferable to TCAs in patients with diabetes.
ADs and psychotherapy may be used in combination to reduce depressive symptoms and to attain glycemic control.
Diabetes Research and Clinical Practice. 2010; 87: 302-312
DEPRESSION & ENDOCRINE DISORDERS
Hypothyroidism and Depression
• Depressive symptoms are common in hypothyroidism
• Many hypothyroid patients fulfill DSM-5 or ICD10 criteria for a depressive disorder
• Depressed patients may be more likely than normal individuals to be hypothyroid
• All depressed patients should be evaluated for thyroid dysfunction
61
Hypothyroidism and Depression
Depression
62
Hypothyroidism
Sleep decreaseSuicidal ideation Weight change Delusions
ConstipationDecreased Conc.Decreased libidoDepressed moodDiminished interestWeight increaseFatigue
BradycardiaCardiac and lipid AbnormalitiesCold intoleranceHair and skin changesDelayed reflexesGoiter
Thyroxine in Depression
1. Thyroxin therapy is recommended for patients with depression who have persistently elevated serum TSH2. Antidepressants may be less effective if thyroid function not normalized
63
• More than 70% of men older than 70 years have free testosterone levels consistent with hypogonadism. Decreased levels of testosterone in men are associated with depression, fatigue, hot flushes, sweating, & weight gain
DEPRESSION & CHRONIC RENAL DISEASE
Depression is the most common psychiatric disorder found in patients with ESRD
A study of patients with CKD stages 2 to 5,with a mean age of 64.5 years, demonstrated a prevalence of major depression to be 21%, with no significant variation between stages
Suicide rates may be 15 times higher than in general population
The diagnosis of depression in pateints with CKD can be complicated, as many of the symptoms seen in CKD such as
1)poor concentration 2)anergia 3)loss of appetite, 4)disturbed sleep 5)decreased libido are also seen in depression
The diagnosis of depression in patients with CKD may be better indicated by
Feeling of helplessness, hopelessness, worthlessness
Suicidal thoughts
Exact etiopathogenesis is unknown Hyper secretion of proinflammatory cytokines in CKD
may play a role via malfunction of noradrenergic & serotonergic neurotransmission in the brain
Endocrine abnormalities such as hyperparathyroidism Functional decline Diminished independence, changes in roles & responsibilities Limitations imposed by dialysis
• The effect of depression itself may have a negative impact on the course of CKD; e.g. decreased oral intake related to depression may worsen the anemia & malnutrition is common in patients receiving hemodialysis
Depression & gastrointestinal disease
• There is a close relationship between gut & the brain, resulting in frequently co-occuring GI disorders & psychiatric disorders
• Clinical epidemiologic studies have shown that approximately 50% of patients with “functional” disorders have co morbid mood or anxiety disorders
• The onset of depression & anxiety tend to occur at approximately the same time as the onset of IBS, suggesting a potentially common etiologic pathway
Depression tend to be seen in patients with more chronic, unremitting illness
The presence of depression predicts a poorer prognosis
In PUD loss of appetite & weight loss are common & can be a result of a number of conditions , including depression
HCV infection provides an excellent example of the 2-way street between medical & psychiatric illness
Patients with HCV are at greater risk for depression On the one hand, infection with HCV can contribute to
depression via multiple mechanisms. Psychologically, it may be depressing to learn that you are infected with the virus & therefore are at risk for complications from HCV
It is typical for patients with HCV to worry that they may have inadvertently infected someone else, including family members, leading to a depressed mood
Furthermore, there is increasing evidence that HCV may directly cause brain changes & may cross the blood-brain barrier, suggesting that the virus may directly contribute to depressed states
HIV AIDS
DEPRESSION DUE TO
Patients with HIV exhibit a higher incidence of depression than general population, with estimations as high as 37%Among drug users with HIV, incidence of depression has been reported to be 70%
One of the reason is poor adherence to antiretroviral therapy in patients
with depression
Neurobehavioral HIV Medicine. 2010; 2: 73-83Ann Pharmacother. 2013; 47: 75-89
Social stigma – is it a cause for depression in HIV?
HIV stigma negatively affects interactions with family, friends, co-workers and health professionals and often results in loss of social supportFear rejection from family and friends
Risk for suicide may be increased when HIV disclosure to loved ones is met with rejection rather than support
Neurobehavioral HIV Medicine. 2010; 2: 73-83
Women living with HIV often associated with the perception of being sexually promiscuous or as vectors for HIV transmission
Nearly 2 decades of research suggest that depression may adversely impact immune function and may accelerate HIV disease
progression.
Use of ADs may improve adherence to antiretroviral medication.
Depressed patients are more likely to use substances that themselves
have negative impact on the immune system
Suicidality and Immunity in HIV patients with depression?
There is an increased risk of suicidal thoughts, attempts and execution of
suicide due to depression in HIV patients
Neurobehavioral HIV Medicine. 2010; 2: 73-83
HIV/AIDS• TCAs as effective as SSRIs, but
limited to second-line and third-line treatment, due to their adverse effect profile
• No data yet available for SNRIs
SSRIs preferable to TCAs.
In small and large group trials, SSRIs have shown a significant reduction in depression scores and symptoms in patients with
HIV.
The major drawback is drug interactions in use with antiretrovirals.
Ann Pharmacother. 2013; 47: 75-89
Anti-depressant Antiretroviral Mechanism Potential Effect
Fluoxetine Protease inhibitors Fluoxetine metabolized by CYP2D6, 2C9, 2C19, 3A4
Increased Fluoxetine levels, potential for serotonin syndrome
Paroxetine Fosamprenavir/ ritonavir
Protein binding displacementInhibition of CYP2D6
Decreased paroxetine levelsIncreased ritonavir levels
Sertraline Protease inhibitors Inhibition of CYP3A4, 2D6
Increased sertraline levelsIncreased ritonavir levels
Citalopram Protease inhibitors Inhibition of CYP3A4 Likely no effect
Escitalopram Protease inhibitors Inhibition of CYP3A4 No effect
Tricyclic antidepressants
Protease inhibitors Inhibition of CYP3A4, 2D6
Increased tricyclic antidepressant levels
Venlafaxine Protease inhibitors Inhibition of CYP3A4, 2D6
Increased venlafaxine levels
Bupropion ritonavir Induction of CYP2B6 Decreased bupropion levels
Ann Pharmacother. 2013; 47: 75-89
Citalopram Protease inhibitors Inhibition of CYP3A4 Likely no effect
Escitalopram Protease inhibitors Inhibition of CYP3A4 No effect
“Citalopram and Escitalopram may be more optimal choices in the context of drug interactions when
administering with antiretrovirals”
CANCER
DEPRESSION DUE TO
Reported Prevalence of Depression in Cancer patients in literature:
Oropharyngeal: 22 – 57%Pancreatic: 33 – 50%Breast Cancer: 1.5 – 46%Lung Cancer: 11 – 44%
Less high prevalence for:Colon: 13 – 25%Gynaecological: 12 – 23%Lymphoma: 8 – 19%
J Natl Cancer Inst Monogr 2004;32:57–71Clinical Practice and Epidemiology in Mental Health. 2007; 3(2): 1-9
Results from an 8-year follow-up study among
10,000 patients:Co-existence of
cancer and depression is
associated with an increased risk
of death- 2006
Depression complicates diagnosis in Cancer patients
• Many symptoms overlap: fatigue, weight loss, loss of appetite, and sleep disruption
• Certain cancer treatment might lead to depressive symptoms
Fatigue is associated with chemotherapy and depression, but both present differently in a cancer
patient.Fatigue in depression includes an emotional
component: demoralized feelings.Fatigue due to chemotherapy does not involve an
emotional component.
Clinical Practice and Epidemiology in Mental Health. 2007; 3(2): 1-9
For cancer patients, being depressed is
normal
MISCONCEPTION:
Research provides only a modest evidence for benefits of pharmacological treatments
SSRIs have been observed to improve the QOL of the patients.
Support Care Cancer. 2007; 15: 123–136
CANCER
SSRIs or TCAs: Medication should be tailored to each patient based on
characteristics of each drug.
Based on evidence and clinical expert opinion, combined treatments most effective
Classes of drugs that may cause depressive symptomsDrug class examples
ACEI Captopril, enalapril, lisinopril
antibiotics Ciprofloxacin ,cycloserine, dapsone,metronidazole, trimethoprim-sulfamethoxazole,amphotericine B, ethionamide
anticholinergics Dicyclomine, scopolamine
antivirals Acyclovir, efavirenz, interferon alfa, nevirapine
barbiturates Phenobarbital, secobarbital
Beta-blockers
BZDs Alprazolam, chlordiazepoxide,clonazepam,diazepam,lorazepam,temazepam,trizolam
CCBs Diltiazem,nifedipine,verapamil
corticosteroids Prednisolone,cortisone,ACTH
Dermatologics Finasteride, isotretinoin
Endocrine modifiers Estrogen,leuorolide
H2 antihistamines Cimetidine,famotidine,nizatidine,ranitidine
NSAIDs Ibuprofen,indomethacin,naproxen,meloxicam
opiods Codeine,meperidine,morphine,oxycodone
Antineoplastic drugs Procarbazine,vincristine,vinblastine,aspraginase
Parkinson drugs Amantadine,levodopa,pramipexole,ropinirole
statins
• When important medical treatments are the etiology of depressive symptoms, the medical team should discuss with the patient the risk & benefit of continuing the offending treatment protocol. Adjunctive antidepressant pharmacotherapy may help when medical treatments cannot be discontinued
When “depression” is not depression at all
I. Hypoactive delirium- it is a common mimic of depression in medically ill patients, as its presenting symptoms- behavioral withdrawal, sleep disturbance, affective flattening & amotivation-overlap closely with a depression
II. Dementia- it can cause a patient to appear amotivated, withdrawn ,affectively blunted
III. Substance intoxication- it can produce a behavioral syndrome that appears consistent with a depressive episode, including suicidal ideation & dramatic emotional posturing
IV. Pain- itself can produce the symptoms of depression when it is untreated or inadequately managed
• Assessment for suicidal thoughts or plan
• Assessment for psychosis – hallucinations or delusions
• Assessment for substances that may cause depressive symptoms such as sedatives, narcotic pain meds, or alcohol
• Association of other conditions that may cause depression or have symptoms in common with depression such as dementia, thyroid problems, or diabetes
• Prior history of depression and response to treatment
Important aspects of managing depression
Special consideration when treating depression in medically ill patients
I. Biological interventions: A)medications: drugs should be chosen to take
advantage of beneficial side effects while avoiding undesirable once & minimizing polypharmacy
B)A common consultation question regards alternate routes of antidepressant administration for patients unable to take pills because of swallowing difficulties, malabsorption, GI obstruction, or NPO status for surgery or other concerns. Unfortunately , most FDA approved antidepressants are available in oral form only
Suggested medications for depression co morbid with prominent physical symptoms
Insomnia- 1st choice -mirtazapine 2nd choice TCAsNeuropathic pain/migraine-TCA or duloxetineFunctional abdominal pain-SSRI or TCAFatigue- bupropion stimulants( methylphenidate,
amphetamines
C) ECT: it can be used safely & successfully. Its advantage is that it acts quickly. ECT can be considered for patients with treatment resistant depression, unremitting suicidality, intolerance to oral medication or NMS
D)TMS: It has shown promise in improving depressive symptoms in patients with various neurological disorders including Parkinson's disease, epilepsy, stroke & has been used safely in pregnant patients
E) Ketamine: emerging data suggests IV Ketamine can be used in rapidly ameliorating treatment resistant depression in emergency rooms
precautions
a) Medically ill patients may be particularly vulnerable to adverse effects of antidepressant medication
b) Hepatic & renal impairment can affect the metabolism & elimination of antidepressant
c) For patients with cardiac disease or those on medications that leads to QTc prolongation, it is important to be sensitive to the potential for further QTc prolongation with many antidepressants
d) In case TCAs the cumulative anticholinergic burden of medications should be considered, particularly when the patient is susceptible to delirium
e) Serotonin syndrome- in medically ill patients the constellation of symptoms may go unrecognized or misidentified as sepsis or anxiety
Psychotherapeutic interventions:
Supportive psychotherapy & problem-solving approaches are useful in depressed medically ill patients
IPT can be readily used in depressed medically ill patients, with a focus on role transition & role disputes that invariably accompany chronic illness
CBT can help patients recognize thought distortions that accompany illness & can also encourage behavioral activation in these patients
• Psychosocial intervention: higher depression risk among family caregivers of medically ill patients is clearly established. In these cases psychosocial intervention may help
ConclusionDepression is not only highly prevalent in chronic illness, but also complicates the underlying cause.
Depression increases the risk of mortality in chronic illnesses.
Depression is associated with poor treatment adherence.
Self-management is often difficult due to cognitive ill-effects of depression
Comorbid depression in chronic illnesses is often misdiagnosed/underdiagnosed and undertreated/mistreated
• Depression associated with medical illness is probably best addressed from a preventive perspective. In some cases, treatment of a medical disorders relieves depressive symptoms as well
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vol36 no.43. Neuropsychiatry of Traumatic Brain Injury, Psychiatric Clinics of North
America,2014 March, vol 37 no 1.4. Frontal lobe dysfunction in secondary depression-journal of
neuropsychiatry & clinical neurosciences, vol6,no 4,19945. Post stroke depression-epidemiology, pathophysiology& biological
treatment-biological psychiatry vol52,issue 3. aug 2002,6. Frontal lobe hypo metabolism & depression in Alzheimer's disease-
neurology,feb 1998,vol 50 ,no27. Prevalence, etiology & treatment of depression in Parkinson disease-
biological psychiatry vol 54 aug 2003
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