Secondary depression: etiopathogenesis & management

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.


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


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


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


Psychological mechanisms linking depression and heart disease - II


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


Psychological mechanisms linking depression and heart disease - II


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


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.



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.



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.


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


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



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.


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

Thank you!

Secondary depression: etiopathogenesis & management

Health & Medicine

Transcript of Secondary depression: etiopathogenesis & management