DIAGNOSIS OF DEPRESSIVE DISORDER IN PATIENTS WITH MEDICAL DISORDERS

DIAGNOSIS OF DEPRESSIVE DISORDER IN PATIENTS WITH MEDICAL DISORDERS

Dr. P. John Mathai

Professor of Psychiatry

FMIMER, Mangalore.

Depressive Disorder is an ubiquitous clinical syndrome which has been described since antiquity. It is a heterogeneous syndrome whose chore clinical features are depressed mood, anhedonia, increased fatigability, psychomotor disturbances, negative cognition and biological (Vegetative) symptoms. It is heterogeneous with regards to biology, treatment response and prognosis.

Evidences from research suggest that a substantial proportion of patients with medical disorders suffer from depressive disorders. All disorders which are not included in Chapter F of ICD-10 or in DSM lV are referred to as medical disorders in that paper. It has been reported that about 5-32 percent of medically ill population as against 4-6 percent of the general population suffer from depressive disorders (Cohen-Cole and Harpe 1987). The onset of depressive disorder antedates the onset of the medical disorder in about 25 percent of patients (Wise and Taylor 1990). There are possibly many significant factors that contribute to the higher documented prevalence of depressive disorders in medically ill patients. These factors will fall into the following four major groups (Wise and Taylor 1990).(1) The biological predisposition of the patient (2) The Psychological responses to the medical disorder (3) The medical disorder as such, its nature and its biological and psychosocial impact on the patient and (4) The medications used for the treatment of the medical disorders. Several investigators report that the diagnosis of depressive disorder is completely missed in about 30-50 percent of patients in the medical setting. (Cohen-Cole and Harpe 1987). One cannot simply blame the astute physicians for this remarkable failure of diagnosis of a disorder which is eminently treatable. It has been well documented that differentiating s depressive-disorder from the expectable mood changes (Sadness, dysphoria, demoralization) due to the medical disorder is problematic for many reasons. Besides there are certain inherent weakness in the very concept of depressive disorder when we deal with patients in the medical settings.

To help us with this conceptional and diagnostic muddle, the most preliminary step could be to avoid the use of the term depression as a synonym for sadness, demoralization, grief and the like. The term depression should be reserved for distinct clinical entities as defined in ICD 10/DSM lV. The depressive response is one of the frequent abnormal reactions to medical disorders like the denial response, the anxiety response, the anger response and the dependency response. Patients who react to medical disorder with depressive response may manifest affective, cognitive and behavioural changes with strong resemblance to those of clinical depression. They very in the degree of severity and the symptoms. Four basic groups of signs and symptoms may be manifest in this response (a) Alterations of affect - sadness, dysphoria, tearfulness irritability and anxiety (b) Physical symptoms due to the physiological sequalae of affective changes (c) Changes in usual patterns of behaviour , withdrawal, mounting preoccupation and retreat from responsibilities (d) Diminished self esteem, negativism, fatigue self reproach and worthlessness. Such responses can complicate the diagnosis, the medical evalution and treatment of the medical disorder. Depressive response can also impede the immunological battle against the medical disorder. A brief discussion (1) on the basic approach to diagnosis of depressive disorder, and (II) the diagnosis of depressive disorder in the medically ill will follow this introduction to this subject.

I. Basic approach to the diagnosis of Depressive Disorder

Once we think of the possibility of a depressive disorder based on the clinical features the basic approach should be to find answers to the following questions, (A) Is the depression within normal bounds or pathological (B) Is it a depressive disorder or other psychiatric disorders like adjustment disorder or anxiety disorder (C) Has it got an organic or toxic basis (D) What is the type of the depressive disorder,

(A) Normal/Clinical Depression

Depression is a normal emotional response to the loss of something valuable to the person. The normality of the emotional state in this context should be judged from the patient's view point against the background of this personality and the nature and severity of the loss. There are no set limits for the normal depressed mood. The boundaries between the normal depression and the clinical depression are foggy and ill defined. The distinction between these to cannot easily be defined with the help of certain concerete clinical criteria. However certain features will very often help us to identify pathological depression. The amplitude, duration or the quality of the depressed mood is such that it is either beyond the adaptive demands or it produces significant impairment in somatic, social and psychological functions. In clinical situations when the distinction is doubtful the best action is to observe the patient with the best possible comfort and reassurance (Hamilton 1989).

B. Depressive Disorder/Adjustment Disorder/Anxiety Disorder

The diagnosis of depressive disorder can be difficult in those patients who are less disturbed, When there are overlap of symptoms and in those with atypical features. One should look specifically for the characteristic clinical features of depression they are (1) depressed mood, (2) loss of interest and anhedonia (3) increased fatiguability and psychomotor retardation (4) reduced concentration and attention (5) reduced self esteem and self confidence (6) ideas of guilt and unworthiness (d) bleak and pessimistic views of the features (e) ideas or acts of self harm or suicide, (f) disturbed sleep (g) diminished appetite (ICD 10). The lowered mood with poor reactivity and diarnal variation is most characteristic. Marked individual variations and a typical features are not uncommon. Anxiety, motor agitation, irritability physical symptoms, like loss of weight, loss of libido, constipation, headache, backache, chest pain, panic attacks, obsessive symptoms, compulsive behaviour depersonalization, de-realization, loss of insight, paranoid features, impulse dyscontrol, sexual dysfunction paraphilias alcohol and substance abuse, hyperphagia, weig gain, hypersomnia cotard's delusion, other delusions and hallucinations, catatonic symptoms, pseudodementia and cognitive impairment are all possible clinical features of depressive disorder. Some of these symptoms are widely regarded as having special clinical significance. They are referred to as somatic symptoms (ICD 10) or melancholic symptoms (DSM IV). They are also known as vital, biological, endgeneous or endogenomorphic symptoms. The somatic symptoms include (1) loss of interest or anhedonia (2) lack of reactivity (3) early morning awakening (4) Diurnal variation depression worse in the morning (5) psychomotor retardation/agitation (6) marked loss of appetite (7) loss of weight and (8) marked loss of libido.

In addition to the characteristic features mentioned the other factors that may help the diagnosis of depressive disorder are (a) the biological symptoms that indicate the deficiency of function (b) the previous history (c) the family history (d) the nature of the stress implicating significant loss and (e) the nature of co-morbidity which is known to co-exit with depressive disorders (Cameron 1990).

Anxiety (Psychic 96% somatic 86%) is very common symptoms in depression disorder (Hamilton 1989). Depressive symptoms are frequently manifest in most of anxiety disorders such as phobic disorder, panic disorder, generalized anxiety disorder and obsessive compulsive disorder. By and large in many clinical situation the distinction between the anxiety disorder and the depressive disorder depends on (1) the clear presidents of one set of symptoms over the other and (2) the definite preponderance of prominence of one set of symptoms over the other. Only when both set of symptoms are severe enough to justify individual diagnosis both shall be diagnosed and recorded. For practical reasons, if only one diagnosis can be made depressive disorder should be given presidents (ICD - 10). The mixed anxiety and Depressive Disorder (F 41.2) should be used only when the symptoms of both anxiety and depression are present but neither set of symptoms considered separately is insufficiently severe to justify corresponding diagnosis.

Adjustment Disorder (43.2) is a subjective distress and emotional disturbance which usually interferes with social functioning and performance. It arises during the period of adaptation to significant life change or life event. This includes the presence or possibility of serious medical disorders. Individual predisposition and vulnerability play significant role in the occurrence and the nature of the clinical manifestations. The onset is fully within one month of the stressful event or life change and the duration dose not usually exceed six months - except in the case of prolonged depressive reaction (not exceeding two years).

The diagnostic guidelines suggested in ICD - 10 are (a) the form content and severity of the symptoms (b) previous history and personality (c) Temporal relationship to stressful / life event / change / erisis (less than 3 months).

Brief Depressive Reaction(43.20)-a transient mild depressive state of duration not exceeding 1 month, prolonged depressive reaction (43.21)-A mild depressive state occurring in response to a prolonged (exposure) to stressful situation but of duration not exceeding 2 years and Mixed Anxiety and Depressive reaction (F23.22) are relevant to the concept of Depressive Disorder.

C. Organic / Toxic Basis

An organic / toxic basis for a psychiatric disorder is considered when there are (1) Atypical features (2) Antecedent factors suggesting organic etiology (3) Significant cognitive deficits (4) Physical / Neurological signs and (5) Evidences from investigations (Mathai 1994). However in the case of depressive disorder even when the diagnosis seems obvious it is wise to consider an organic / toxic basis. This is because a typical depressive disorder can be secondary to medical disorders or medications or can coexist with a medical disorder. Selective lists of common medical conditions and drugs that can cause / induce / coexist with depressive disorder (Organic Mood Disorder Depression Secondary Depression) are given in Table A and B respectively. The diagnosis which are often missed despite best clinical efforts are hypothyroidism diabetes, melitus early Parkinsonism, early dementia, cerebral arteriosclerosis, IC SOL,Vit, 812 deficiency, electrolyte, imbalance, TBM and drug induced states (Mathai 1994). Research evidences and clinical experience suggest that about 10-20 percent of patients who meet the clinical criteria for major depression or dysthymia actually have undiagnosed medical disorder or drug induces syndromes.

D. Types of Depressive Disorder

It is conventional to conclude whether a depressive disorder is Bipolar / Unipolar, Endogenous / Reactive, Psychotic / Neurotic, Primary / Secondary, Typical / Atypical and single episode/ Recurrent. Most of these classical dichotomies are given adequate significance in the current diagnostic systems like the ICD-10 and the DSM-lV (Table C,Table D).

The ICD-10 Incorporating most of these essential dichotomies has fewer types of depressive disorders than ICD-9 (Table C). Single episodes have been distinguished from recurrent episodes and unipolar from bipolar. The depressive episode is further classified based on the severity (mild, moderate, sever) the presence of somatic symptoms (at least 4 of the somatic symptoms) and the presence of psychotic symptoms (delusions, hallucinations or stupor). If required the delusions and hallucinatins may be specified as mood congruent or mood incongruent. Again the persistent depressive disorder is distinguished from the episodes and provisions for atypical and unspecified varieties have been provided (F 32.8, 32.9, 33.8, 33.9, 38, 41.2). For the diagnosis of mild depressive disorder at least 2 of the typical symptoms plus at least 2 of the other symptoms and at least 2 weeks duration should be present. For moderate depressive disorder 2+3(4) and 2 weeks and for severe depressive disorder 3+4 and 2 weeks should be present for diagnosis. If the symptoms are particularly severe and the onset is very rapid a diagnosis of moderate and severe depressive disorder is justified even if the duration is less than 2 weeks.

Differential Diagnosis

The differential diagnosis for Depressive Disorder include

a) Organic Mood Disorder - Depression

b) Dementia with depressive symptoms

c)Delirium with psychomotor inhibition

d) Adjustment Disorder

e) Alcohol and substance abuse / dependence

f) OCD

g)Anxiety

h) Sexual Disorder

i) Somatoform Disorder

j) Schizophrenia Schizoaffective disorder and Delusional Disorder

k) Personality Disorder

l) Others

The laboratory tests (biological markers ) though potentially useful does not have adequate specificity to depend entirely on then for differential diagnosis in clinical practice (Kaplan et al 1994, Kendell 1993).

PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF DEPRESSIVE DISORDER

The development of the diagnostic dirteria and the structured clinical interviews have indeed contributed to the better reliability of depressive disorders. The are still many problems associated with the diagnosis of depressive disorder some of which will be briefly discussed.

1. Reliability :

The reliability of diagnosis is reduced by several sources of variance such as subject variance, occasion, variance, information variance and the criterion variance (Spitzer et al 1978).The impact of these sources of variance can be reduced markedly in modern clinical practice with structured interviews, standard information and definitions, interviewing both patient and relatives at least for more than one occasions and operationalized diagnostic criteria. It has been documented that there has been a remarkable increase in the reliability of psychiatric diagnosis of major categories including depressive disorder since the introduction of DSM III (0.41- 0.77 to 0.65- 0.83). But by no means the reliability is absolute although it is satisfactory.

2. Validity :

The diagnosis of depressive disorder has adequate face and descriptor validity has at present serving the purpose of communication. Its predictive validity and construct validity are not satisfactory. Investigations using laboratory tests like DST and clinical factors like treatment response, family history and causes of illness do not indicate that in general the diagnosis of depressive disorder has adequate predictive validity. This is debatable issue.

3. Syndrome /Disorder:

The term disorder has replace the use of the term syndrome in the context of depression. The term disorder indicates that a pathological process is known or suggested and it is implied treatment selection and prognostcation are made possible. At the same time it has been well documented that depressive disorder is heterogeneous with regards to its etiology, biology, tratment response and prognosis. In the absence of adequate predictive validity, construct validity and external validators like laboratory tests do we have enough to call it as depressive disorder.

4. Medically ill Population:

The diagnostic criteria in ICD - 10 and DSM IV are for patients with exclusively psychiatric disorders. They are not standardized in medically ill population and there reliability and validity in this special populations is not established.

5. Basis for Diagnosis

There are several bases for validating a diagnosis category. They include etiology, symptomatology, course, pathogenesis and treatment response. The basis for diagnosis of depressive disorder largely depends as signs and symptoms. Hence on must be aware that age, sex, personality and host of other variables will affect the clinical presentation and consequently the diagnosis.

6. Diagnostic Criteria

All the diagnostic criteria for diagnosis of depressive disorder are not specific to that disorder. In practice it is really difficult to differentiate a depressive disorder from anxiety disorder and adjustment disorders. A clinical distinction between primary and secondary (organic depressive disorder) basically depends on the assumption or judgement of an etiologically related organic factory (Medical disorder/ medication) to the depressive syndromes (Fogel 1990). Further many of the criteria like depressed mood, fatigue, loss of appetite, sleep disturbance, loss of weight and libido are very common in certain medical disorders.

7. Descriptive Diagnosis

Various factors related to patient, physician, socio-cultural and medical background may often confound and complicate the diagnosis of depressive disorder. T=Most of them are listed by Rush (Rush AJ 1988, 1990- Table E)

8. Sub-classification of Depressive Disorder

Sub-classification of depressive disorder is based on prior history of the disorder (bipolar /unipolar, seasonal/ nonseasonal, chronic/ nonchronic) or on the cross- sectional clinical symptoms picture (mild/ moderate severe, somatic symptoms, psychotic symptoms, atypical symptoms). This attempt to divide depressive disorder largely rests on the notion that it will be of general and specific predictive value for prognosis and treatment response. This notion requires further evaluation and research evidences in support. There are certain evidences to support Melancholia somatic symptoms (ECT, Antidepressants ) and atypical features (MAOI), psychotic symptoms (ECT, Antipsychotic) and rapid cycling lithium, carbamazepine.

Depressive Disorder is an eminently treatable disorder. But it is often undiagnosed or misdiagnosed. The diagnostic accuracy can be improved. And as the range of effective treatment broadens diagnostic accuracy become more vital.

II. DIAGNOSIS OF DEPRESSIVE DISORDER IN PATIENTS WITH MEDICAL DISOREDERS:

The assessment and diagnosis of depressive disorder in patients with medical disorders are problematic for tow fundamental reasons. First the dyphoria or sadness is an acknowledged part of the experience of medical disorders. An already mentioned the boundary between the expected affective response and the pathological depression remains arbitrary. Secondly many of the symptoms of medical disorders are identical to those of depressive disorders. anorexia, Insomnia constipation loss of weight, decreased energy, fatigue and loss of libido are striking examples. The clinical finds in difficult to determine the basis of origin of such identical symptoms.

Approaches to the evaluation of depressive symptoms in patients with medical disorders:

Because of the two fundamental problems mentioned the evaluation of depressive symptoms in patients with medical disorders is exceedingly complex. Unfortunately the literature does not provide use with clear answers regarding (1) the practical criteria to distinguish between the normal affective response and clinical depression and (2) practical guidelines for interpretation of the identical symptoms. To date there are four major approaches to the diagnosis of depressive disorder (major depression) in the medically ill. These are termed (1) inclusive (2) Etiologic (3) Substitutive and (4) Exclusive approaches (Cohen - Cole and Harp 1987)

1.Inclusive Approach:

This is the simplest approach. The investigators used SADS and RDC,. All depressive symptoms irrespective of the contribution from or attribution to the to the medical disorders are counted for diagnosis (Rifkin et al 1985).

This method is conceptually clear and clean. This is in keeping with the descriptive alteoretcial philosophy of modern systems of classification (DSM III, IV, ICD 10). This is likely to have good inter rater reliability. But this good lead to over diagnosis. Its sensitivity should be high, but it specificity should be lower.

2. Etiologic Approach

The approach is advocated by Spitzer et al (1984). This approach suggests that the depressive symptoms should be counted only if it is "not clearly due to a physical illness". This is decision rule followed in SCID and DIS. But it is not specified how this decision is clinically made.

This method is conceptually unclear and unclean. It requires inference of casualty. Hence its inter rater reliability should be lower. It is possible that some psychiatrists working in very specific medical settings might become experienced to distinguish the basis of the idential symptoms reliably. But for the general psychiatrist it would be impossible to do so in a reliable manner. The validity of this method remains uncertain.

3.Substitutive Approach

This approach suggests modification of the criteria which is not suitable in the context the medical disorder (Cavenagh et al 1983, Clerk et al 1983, Endicott 1984). for example decreased energy poor discriminator may be replaced by indecisiveness, brooding self pity or pessimism. It is not clear whether this approach would lead to over under diagnosis of depressive disorder. The advocates of the method does not indicated the source of the substitutive criteria to be used.

4.Exclusive Approach

This approach eliminated identical symptoms from the diagnostic criteria (Plump and Holland 1981, Buckberg et al 1984). For example in their research on depression in cancer patients they eliminated anorexia and fatigue and the criteria for diagnosis was reduced from 5/9 to 4/7 for major depression

Like the inclusive approach, this is relative clear and clean. This should have good inter rather reliability and probably high specificity the cost of long sensitivity

Clinical Evaluation of Diagnosis:

These four approaches have specific advantages depending on the definite objectives. For research purpose the best is the exclusive approach with high specificity. But for clinical use it is to exclusive. For clinical use the best available is probably the inclusive approach with of course modification based on clinical judgment. The etiologic approach is theoretically sound but practically difficult to implement. The substitutive approach is conceptionally reasonable but the experience is to little to be used in clinical practice.

Depressive disorder is generally under diagnosed in the medically ill, Maximizing the sensitivity is the most important step for the clinician. Hence the inclusive approach is the best available approach for clinical evaluation. The skilled doctor does not rely entirely on the application of the criteria in a mechanical way for diagnosis. The use of diagnostic criteria does not eliminate clinical judgment. In the medically ill the doctor should pay particular attention to the psychological symptoms of depression and anhedonia (Table F). A thorough evaluation of these patients requires a multidimensional approach. This should include the following elements (1) Clinical signs and symptoms (2) Previous history of depression (3) Previous response to treatment (4) Family history of affective disorder (5) Response to treatment of the most recent episode ND (6) Biological markers-(DST, TRHST, RLT). These factors may help the diagnosis of depressive disorder in the medically ill patients (Cameron 1990). Finally in the clinical diagnosis of depressive disorder in the medically ill certain factors should be given practical importance. Firstly keep common things as common. Secondly, depressive disorder should be diagnosed by commission and not by omission. Thirdly the diagnosis of masked depression is better avoided or made with great caution. Fourthly remember that multiple medical and multiple psychiatric disorders may coexist in the same patient. And finally when there is substantial diagnostic uncertainity a trial with a safe antidepressant is warranted.

CONCLUSION :

The depressive disorders are common in patient with medical disorders. The diagnosis of depressive disorder in a substantial proportion of medically ill is not made. There are many problems associated with the diagnosis of this disorder particularly so in the medically ill patients. Unambiguous criteria for the diagnosis of the disorder in the medically ill does not exist. The ICD-IV does not have established reliability and validity in this special population. The research in this area in inadequate at present. Many questions remain unanswered. It is possible that the clinical research will provide us with important clues for the unanswered questions at the interface of depressive disorder and medical disorders.

TABLE - A
SELECTIVE LIST OF MEDICAL DISORDERS ASSOCIATED WITH DEPRESSIVE DISORDER
1. Carcinoid Syndrome
2. Carcinoma Pancreas
3. Stroke
4. Collagen Vascular Disease (SLE)
5. Endocrinopathies, Cushing's Syndrome, Addison's Disease, Hypoglycemia Hyper and Hypocalcemia, Hyper and Hypothyroidism.
6. Lymphomas
7. Parkinson's Disease and Parkinsonian Syndrome
8. Bernecious annemia
9. Viral infection, Hepatitis, Mononucleosis, Influences, EB Virus infection
TABLE - B
SELECTIVE LIST OF MEDICATIONS ASSOCIATED WITH DEPRESSIVE DISORDER
1. Anti hypertensives - Reserpine, Methyldopa, Clonidine, Calsium Channel inhibitors, Propranolol
2. Barbiturates
3. Cimetidine
4. Cortico stergids/oral contraceptives
5. Indomethacin
6. Pentazocine
7. Levodopa
8. Ethionamide, Prothionamide
9. Antipsychotics
10.Vincristine, Vinblastine, Other antimetabolites.
TABLE - C
THE ICD - 10 DEPRESSIVE DISORDERS
1. Bipolar Depressive Disorder
Mild/mod'erate with/without somatic symptoms		31.31
		31.30
Severe with/without psychotic		31.35
		31.34
Mixed		31.60
2. Depressive Episode (F32)
Mild with/without somatic symptoms		32.01 32.00
Moderate with/without somatic symptoms		32.11 32.10
Severe with/without psychotic symptoms		32.3 32.2
Others-Atypical Depression		32.8
Depressive Disorder(Nos)		32.9
3. Recurrent Depressive Disorder(F33)
Mild/Moderate, with/without somatic symptoms		33.00 33.01
		33.10 33.11
Severe with/without psychotic symptoms		33.33 33.32
RDD in Remission		33.4
RDD Others		33.8
RDD (NOS)		33.9
4.Persistant Depressive Disorder(F34)
Dysthymia		34.1
Others persistant mood disorder		34.8
5. Other mood disorders F(38)
Mixed Affective Episode		38.00
Recurrent Brief Depressive Episode (RBDD)		38.10
6. Mixed Anxiety and Depressive Disorder (F 41.2)
TABLE - D
THE DSM-IV-DEPRESSIVE DISORDER
1.	Major Depressive Disorder Single Episode	296.2
2.	Major Depressive Disorder Recurrent	296.3
3.	Dysthymic Disorder	300.4
4.	Depressive Disorder (NOS)	311.0
5.	Bipolar l-Disorder-Most recant Episode Depressed	296.5
6.	Bipolar l-Disorder-Most Recant Episode Mixed	296.6
7.	Bipolar ll Disorder
8.	Mood Disorder due to general medical condition with Depressive Features and with Major Depression like episode
9.	Substance Induced mood Disorder with depression with onset Drug Intoxication / withdrawal
SPECIFIERS OF THE DEPRESSIVE EPISODE
a).	Severity - mild, Moderate, Severe
b).	Psychotic Features- without/with mood congruent/incongruent Psychotic features
c).	Remission- partial remission/full remission/unspecified
d).	Chronic specifier (2 years).
e).	With Catatonic Features.
f).	With Melancholic Features.
g).	With Atypical Features.
h).	With Post partnem onset.
i).	Longitutinal course specifier - with full inter episode recovery/without full inter episode recovery.
j).	With Seasonal pattern.
k).	With Rapid cycling.
TABLE - E
DIFFICULTIES IN DESCRIPTIVE DIAGNOSIS OF DEPRESSIVE DISORDER
A. Patient Factors:
Age, SE Class, Negative Cognition, Eroneous Anamnesia, Problem, Disorientation
B. Physician Factors:
Focus on one or two symptoms, Attribution of cause to life event, Premature symptomatic drug prescription, Failure to interview relatives. Overeliance on Laboratory tests. Under utilization of Psychiatric consultation. Failure to use criteria.
C. Socio cultural Factors:
Stigma and denial Erroneously viewed life stresses. Complication of Depression Blaming social/religious systems
D. Medical Factors:
On psychotropic medication Coexistant medical disorders on other medications episodic nature of depressions personality
TABLE - F
A. General symptoms
1. Depressed mood
2. Loos of interest/anhedonia
B. Physical symptoms
1. Reduced energy and increased fitguablty
2. Psychomotor retardation/agitation
3. Disturbed sleep
4. Altered Appetite
5. Loss of weight
6. Marked loss of libido
C. Psychological symptoms
1. Reduced concentration and attention
2. Reduced self esteem and self confidence
3. Ideas of guilt and unworthiness
4. Bleak and pessimistic view of the future
5. Ideas or acts of self harm or suicide (ICD 10, DSM IV)