Asian Journal of Psychiatry 6 (2013) 338–343

Untreated major depressive disorder with and without atypical features:A clinical comparative study

Sharmishtha Deshpande *, Poonam Patil, Bhalchandra Kalmegh, Madhav Ghate

Dept. of Psychiatry, Smt. Kashibai Navale Medical College and General Hospital, Narhe, Pune 411041, India

A R T I C L E I N F O

Article history:

Received 12 July 2012

Received in revised form 27 October 2012

Accepted 5 December 2012

Keywords:

Atypical depression

Soft bipolar disorders

Untreated depression

A B S T R A C T

Aims and method: A comparative study of major depression with and without atypical features (as per

DSM IV TR criteria) was planned to assess illness characteristics, resulting dysfunction and co-

morbidities, which can have important implications in its management. Serially, 107 newly registered

patients with depression not taking any treatment for at least a month were included. Patients with

psychotic features in present or past, known bipolar disorder and likely organic aetiology were excluded.

They were interviewed using SCID I (Structured clinical interview for DSM IV axis I disorders).

Impulsiveness, suicidal ideation and functioning in various spheres was also assessed and compared

between those with and without atypical features.

Results: Atypical features were seen in a significant number (55.14%) of patients especially from urban

and semi-urban areas. Interpersonal sensitivity and leaden paralysis were the commonest atypical

features apart from mood reactivity. Presence of hypersomnia and/or hyperphagia documented in 36

(33.65%) of 107 patients. Comparison of patients with and without atypical features revealed no

significant difference in illness characteristics including suicidal ideation. However, they differed in level

of impulsiveness and associated psychiatric co-morbidities. Also, deterioration of functioning with rising

HDRS was more significant in patients without atypical features.

Clinical implications: Presence of atypical features is common in patients with major depressive disorder.

These patients should be vigilantly assessed and managed in view of equal morbidity but different co-

morbidities like anxiety and soft bipolar disorders than those without atypical features.

� 2012 Elsevier B.V. All rights reserved.

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1. Introduction

The incidence of depression is on the rise in all communities.Depression is expected to be the top most cause of disability allover the world by 2020. Overall lifetime prevalence of depressionin the community is expected to be 10–12% (WHO, 2001) or higher(Kessler et al., 2003) and would cause significant role impairment.Clinical presentation of these patients is varied, affected by theirpersonalities, intelligence, social situation and also some culturalfactors. During clinical interaction with patients, one can delineatethe sub-groups of these patients.

Atypical features and melancholic features have been enlistedas episode specifier in DSM IV TR. Atypical features of depressionhave been included as episode specifier in DSM IV since 1994 (APA,1994). They include reactivity of mood along with two of the four

* Corresponding author.

E-mail addresses: sharod@rediffmail.com (S. Deshpande),

poonamnpatil@gmail.com (P. Patil), bhalchandrakalmegh@yahoo.com

(B. Kalmegh), mrghate@rediffmail.com (M. Ghate).

1876-2018/$ – see front matter � 2012 Elsevier B.V. All rights reserved.

http://dx.doi.org/10.1016/j.ajp.2012.12.002

features – hypersomnia, interpersonal sensitivity, leaden paralysis,and increased appetite or weight.

Some researchers have considered presence of hypersomniaand/hyperphagia as atypical features of depression (Blanco et al.,2011; Parker et al., 2002). We have considered the DSM IV TRdefinition of atypical features for this study. This definitionrequires preserved mood reactivity as the basic feature. Manyresearchers have expressed their views and documented somedifficulties in DSM IV definition of atypical features. However, thisdistinct subtype of depression has been extensively studied andpartially validated (Posternak and Zimmmerman, 2002; Singh andWilliams, 2006). Yet, no such study conducted in India could betraced by the authors. Clinicians may often underestimate severityof depression in the presence of atypical features, miss out onbipolarity and treat these as anxiety disorders, as diagnosis isseldom systematically established in routine psychiatry practice.

There is a volume of research done with bipolar disordersrecently discovering rise in its prevalence figures due to broadeneddefinitions. However, difficulty lies in identifying the depressivecomponent of bipolar spectrum disorders. Literature review ofDSM IV TR has concluded that atypical depression is more common

S. Deshpande et al. / Asian Journal of Psychiatry 6 (2013) 338–343 339

in bipolar II and other soft bipolar spectrum disorders (APA, 2005;Singh and Williams, 2006).

A comparative study of depression with and without atypicalfeatures was thus undertaken to elaborate on varied clinicalpresentations in patients with major depression.

2. Method

This was a cross-sectional hospital-based study of patientssuffering from major depressive episode or disorder (MDE orMDD). The study was conducted in the psychiatry clinic of atertiary hospital. All the consecutive patients newly registered andnot on any treatment for at least a month were considered forinclusion in the study. This was helpful for studying symptom-atology, which would change after starting of any treatment;enrolling consecutive patients would avoid selection bias. Thoughnewly registered, many had suffered from depression in the past orhad dropped out from treatment. Those between the ages of 18 and60 years were included. Patients likely to have depressionsecondary to general medical condition were excluded. Patientswith history suggestive of manic episode or psychotic features inthe past were excluded.

Permission of an Institutional Ethical Committee was obtained.Patients were given an information sheet to read and then awritten informed consent form to sign if they agreed to participate.Four declined to participate, which was either due to timeconstraint or stigma.

Over a period of six months, data of 107 patients wereinterviewed by authors (SD, PP, BK). Each patient with clinicalfeatures of MDD was administered SCID I Research version (Firstet al., 2002) to confirm diagnosis of MDD and/or dysthymicdisorder and also to look for other co-morbidities. The patient wasthen scored on HDRS (17 item scale) (Hamilton, 1960), Barrett’simpulsivity scale (Patton et al., 1995), Paykel’s scale (Paykel et al.,1974) and other information in the semi-structured format.Presence of atypical features, ongoing and precipitating stresses,sexual history and evaluation of functioning using GAF (Globalassessment of functioning scale), SOFAS (Social and OccupationalFunctioning Assessment Scale) and GARF (Global Assessment ofRelational Functioning scale) (APA, 1994) was the other informa-tion recorded. These have been reported as valid scales forassessment of axis V of DSM IV (Hilsenroth et al., 2000; Mello et al.,2007). These would indicate overall functioning of the individualalong with assessment of his functioning in social occupational andinterpersonal relationships domain. Semi-structured question-naire to assess these had been developed and used earlier by

Table 1bRelative proportions of patients with atypical features: DSM IV TR criteria versus prese

DSM-IV TR criteria (N = 107) Hypersomnia and/or hyperphagia

Yes (n = 36)

Yes (n = 59) 34

No (n = 48) 2

Table 1aFrequencies of atypical features (DSM IV).

Atypical feature (N = 107) Frequency in MDD with ATF

Mood reactivity 59 (100%)

Hypersomnia 25 (42.4%)

Interpersonal sensitivity 55 (93.2%)

Leaden paralysis 49 (83%)

Increased appetite or weight 16 (27.1%)

a ATFS, atypical features as per DSM IV TR criteria.

author (SD) (Gaikwad et al., 2006). Family history and history ofself-harm in the past was documented as per the format.Interviewing was expected to take about 90 minutes.

The treatment of the patients was started and continued like allother patients in the OPD.

Data obtained was entered in Microsoft Excel sheets. Biomedi-cal Data processor (BMDP 2.0) was used by expert statistician forstatistical analysis. Patients with and without atypical featureswere compared using non-parametric tests to find out thestatistically significant differences between the groups.

3. Results

Atypical features specifier questions were administered to all107 patients, 59 out of which (55.14%) qualified for same. Thefrequencies of various atypical features are tabulated in Table 1a.

We see that symptoms of hypersomnia and hyperphagia aremore specific for depression with atypical features group, whereassymptoms of interpersonal sensitivity and leaden paralysis areseen in either group.

If we consider presence of hypersomnia and/or hyperphagia ascriteria of atypical features, 36 out of 107 (33.64%) patients hadthese. They belonged mainly to the group of patients with DSM IVspecified atypical features’ group. Analysis (Table 1b) shows onlytwo patients (out of 48) without mood reactivity had hypersomniaand/or hyperphagia (x2 = 31.5306, P = 0.00000) and thus thisdefinition of atypical features may be a subgroup of broadercriteria specified in DSM IV TR.

The sample consisted of mostly adult married people fromlower socio-economic class (Table 2). Most of them had receivedschool education and had varied occupations. Urban, semi-urbanand rural population of various ages was well represented in thesample.

Presence of atypical features did not differ across various socio-demographic factors except residence.

Depression with atypical features was associated with signifi-cantly more impulsivity as measured by Barrett’s scale (Table 3).Patients with atypical features may be expected to haveimpulsivity more than those without as they often lack psycho-motor retardation and have mood reactivity and interpersonalsensitivity. However, difference in motor impulsivity was mainlyfound to be statistically highly significant. The items includedunder motor impulsivity mainly include acting on the impulse as inchanging job or residence or buying things, etc.

There was little difference in illness severity as seen by HDRSscore or suicidal ideation as seen in Paykel’s score across the two

nce of hypersomnia and/or hyperphagia.

No (n = 71) Chi-square (x2) P

25 31.5306 0.0000

46

Sa (n = 59) Frequency in MDD without ATFSa (n = 48)

0 (0%)

2 (4.1%)

29 (60.4%)

13 (27%)

0 (0%)

Table 2Various socio-demographic factors in patients with major depressive disorder with and without atypical features.

Socio-demographic factor MDD with ATFS (N = 59) MDD without ATFS (N = 48) Chi-square (x2) P-value and statistical significance

(1) Age

18–30 years 26 19 0.2184 0.6402, not significant

31–60 years 33 29

(2) Sex

Male 25 16 0.9150 0.3387, not significant

Female 34 32

(3) Residence

Urban 37 16 9.2597 0.0097, highly significant

Semi-urban 12 19

Rural 10 13

(4) Education

Illiterate 9 11 1.7370 0.6287, not significant

Up to 7th 15 11

8th to 12th 31 21

Graduate and above 4 5

(5) Marital status

Married 40 36 1.4281 0.4896, not significant

Divorced/separated/widowed 5 5

Unmarried 14 7

Table 3Impulsivity and atypical features in major depressive disorder.

Impulsivity and its sub-type With atypical features Without atypical features Independent

samples ‘‘t’’

P-value and statistical

significance

Mean S.D. Mean S.D.

Barrett’s total score 70.84 15.8 65.93 14.05 �1.6820 0.0955, marginally significant

Attentional (AI) 20.15 4.9 19.06 4.7 �1.1646 0.2468, not significant

Motor (MI) 24.76 6.5 20.97 5.3 �3.2581 0.0015, highly significant

Non-planning (NpI) 25.89 7.0 25.64 6.7 0.1886 0.8507, not significant

Table 4HDRS and scores of level of functioning in major depressive disorder with and without atypical features.

Score ATFS Without ATFS Independent

samples ‘‘t’’

P-value and

statistical significance

Mann–Whitney

test statistic

P-value and statistical

significance

Mean S.D. Mean S.D.

HDRS total 20.25 5.2 21.96 6.0 1.5537 0.1232, not significant 1690.0 0.0827, marginally significant

GAF 59.0 9.5 56.25 9.0 �1.5283 0.1294, not significant 1050.0 0.0186, significant

SOFAS 57.8 9.2 57.0 7.8 �0.4269 0.6702, not significant 1250.0 0.2874, not significant

GARF 52.62 13.5 52.60 11.4 �0.0093 0.9925, not significant 1450.0 0.8519, not significant

Paykel’s score 1.0847 0.84 1.0416 0.99 �0.2441 0.8075, not significant 1340.0 0.6088, not significant

Spearman’s correlation coefficient ‘‘r’’

ATF present ATF absent

HDRS � GAF ‘‘r’’ = �0.1698 ‘‘r’’ = �0.4515

‘‘P’’ = 0.0994, marginally significant ‘‘P’’ = 0.000006, highly significant

‘‘n’’ = 59 ‘‘n’’ = 48

HDRS � GARF ‘‘r’’ = �0.3018 ‘‘r’’ = �0.3160

‘‘P’’ = 0.0101, significant ‘‘P’’ = 0.0143, significant

‘‘n’’ = 59 ‘‘n’’ = 48

Table 5Duration of illness and atypical features.

Duration of illness (in months) With atypical features Without atypical features Chi-square (x2) P-value and statistical significance

Total

Less than 1 year 26 21 0.4072 0.8157, not significant

1–5 years 26 23

More than 5 years 7 4

Current duration

Less than 6 months 32 28 1.8030 0.6142, not significant

7 months to 1 year 17 10

1–2 years 5 3

More than 2 years 5 7

S. Deshpande et al. / Asian Journal of Psychiatry 6 (2013) 338–343340

Table 6Co-morbid psychiatric diagnosis in patients of major depressive disorder with and

without atypical features.

Psychiatric diagnosis With atypical

features (n = 59)

Without atypical

features (n = 48)

Hypomanic episode 3 0

Cyclothymic disorder 2 0

Hyperthymic disorder 4 0

Generalized anxiety disorder 3 0

OCD 1 0

Social anxiety disorder 1 0

Pain disorder 4 0

Dysthymic disorder 11 5

Presence of melancholic features 0 23

S. Deshpande et al. / Asian Journal of Psychiatry 6 (2013) 338–343 341

groups. Other illness characteristics like duration of illness,number of episodes were also comparable (Tables 4 and 5).

The clinical differentiation of this subtype of depression isseldom a routine practice. However, in view of preserved reactivityof affect the severity of depression and suicide risk may beundermined in these cases. Overall impairment of functioning wassimilar in those with and without atypical features (Table 4).

Severity of depression was grossly comparable between the twogroups. However, deterioration of functioning with rising HDRSscore (Spearman’s correlation coefficient) was significantly morein depression without atypical features, though deterioration inrelational functioning (GARF score) was comparable to someextent.

Total and current duration of illness was comparable across thetwo groups, though co-morbid diagnosis of dysthymic disorderwas more common in depression with atypical features.

Many of the patients with atypical features had co-morbiddiagnoses of anxiety, somatoform and bipolar spectrum disorders(Table 6). We can consider these as two distinct sub-groups of co-morbidities. Further research may highlight if they corroboratewith the two definitions of atypical features – DSM IV criteria andpresence of hypersomnia and/or hyperphagia.

4. Discussion

4.1. Socio-demographic comparison

We found no difference in frequency of the presence of atypicalfeatures across age or sex as against that mentioned in theliterature. Atypical features have been reported to be morecommonly associated with female gender, early onset depression,family history of bipolar disorders and depressive mixed states(Parker et al., 2002; Benazzi, 2005). We also grouped data as permarital status and gender. However, the difference was notstatistically significant.

We see that a significantly higher number of urban patients hadatypical features than semi-urban or rural population (P = 0.0097).The variety of pleasurable activities available in an urban settingcan be one reason for maintenance of mood reactivity. Also, lessinterpersonal tolerance seen in the urban setting can be due tomore individualistic thinking and nuclear families. Low prevalencein rural setting could be due to poor rate of help seeking on accountof preserved mood reactivity of rural patients, but needs to beexplored by further research. Nonetheless, as seen in this table,educational status of the individual was not related to the presenceof atypical features. The study population was representative of allage groups, both genders and various educational levels.

4.2. Clinical comparison

Depression with atypical features as per DSM IV TR seems to bea common presentation of depression in an Indian setting. It waspresent in 59 out of 107 (55.1%) of these patients. Preserved moodreactivity was seen in patients with varying severity of depression.Considering controversies in defining atypical depression, we alsoconsidered the number of patients with hypersomnia and/orhyperphagia. Atypical features were present in 36 out of 107patients (33.65%) when we considered this definition (Blanco et al.,2011; Posternak and Zimmerman, 2002). Thirty four of these(94.4%) also fulfilled DSM IV criteria. A broader group of patientswith atypical features as per DSM IV criteria were thus taken forfurther analysis.

Apart from reactivity of mood, the two other atypical featurescommonly reported were interpersonal sensitivity reported by 84out of 107 (78.5% patients) and leaden paralysis, which arecommonly seen in anxiety disorders (Table 1). Depression with

prominent anxiety features has been documented as commonfinding in Indian setting (Trivedi et al., 2010). These interpersonalsensitivities leading to problems in relationships are among thecommon precipitating cause of suicide in India (Vijayakumar,2010). Interpersonal sensitivity has been defined as ‘‘long standingpattern of interpersonal rejection sensitivity (not limited toepisodes of mood disturbance) that results in significant socialor occupational impairment’’ (First et al., 2002). This was verycommon in this group of patients as seen from these results.Interpersonal stress was also reported as one of the commoneststresses by this group of patients. Forty out of 66 females reportedvarious problems with primary support group, majority of whichwere interpersonal in nature. Managing interpersonal stressesshould be an integral part of management of depression.

Various psychiatric disorders including depression as well aspersonality disorders are known to be associated with increasedimpulsivity. Those with history of prior suicide attempts have beenreported to have higher impulsivity (Wu et al., 2009). Past historyof suicide attempts was reported by 10 out of 59 patients withatypical features (16.9%) and 8 out of 48 (16.6%) patients withoutatypical features. In the absence of psychomotor retardation,depression with atypical features seems to be associated withmore motor impulsivity (Table 3). However, comparable suicideideation score on Peykel’s scale (Table 4) may lead to increased riskof attempting suicide in these patients.

Whether personality of an individual is also contributory indetermining the presence of atypical features as well asimpulsivity is being researched by investigators as a continuationof this study.

Global functioning was more impaired in those withoutatypical features. This could be due to psychomotor retardationin these patients.

This probability is strengthened by finding the extent ofnegative correlation (by Spearman’s correlation coefficient)between rising levels of HDRS and falling levels of functioningscores (GAF and GARF). Functioning deteriorated with rising HDRSscore much more in the absence of atypical features than whenatypical features were present (Table 4).

We can see more co-morbid psychiatric disorders in patients ofMDD with atypical features than those without atypical features.As expected, melancholic features were seen predominantly inpatients without atypical features (Table 6). Nine of them hadbipolar disorder (hypomanic episode, cyclothymic disorder,hyperthymic disorder) (15.2%).

None of the patients without atypical features had any of thesedisorders, which is worth noting.

Presence of co-morbid anxiety and pain disorder was equallyassociated with the presence of atypical features (9 out of 59, i.e.15.2%) and none of the patients without atypical features had theseco-morbidities. Co-morbidity of depression with atypical featureswith social phobia, panic disorder with agoraphobia and poor

S. Deshpande et al. / Asian Journal of Psychiatry 6 (2013) 338–343342

response to tricyclic anti-depressants has been reported in theliterature (Benazzi, 2005). Anxiety disorders are often co-morbidwith depression in India, which often increases the dilemma indiagnosis of depression (Trivedi et al., 2010).

Presence of melancholic features was much more common inthose without atypical features. This is expected as it requires lossof pleasure in almost all activities, or lack of reactivity to usuallypleasurable stimuli as the basic criterion.

4.3. Management implications

Major depressive disorder causes significant disability for theindividual and distress to the family. Twenty nine to forty sixpercent of patients are known to exhibit partial or no response totreatment with antidepressants (Fava, 2000). Poor response totreatment is more frequent in bipolar than unipolar depression.Long term effectiveness and safety of use of antidepressants inbipolar depression has not been established (Ghaemi et al., 2004).Antidepressants have a limited role in depressive mixed states andmay be harmful if continued beyond remission of symptoms as byinducing rapid cycling in the bipolar group of these patients(Ghaemi et al., 2010). Also, these patients are found to have pooradherence to treatment which may be attributable to their rapidimprovement in symptoms (Roy et al., 2010). As atypical featuresare often seen in bipolar depression and its syndromal boundarywith melancholic depression is less prominent than initiallyhypothesized (Thase, 2007), this study was undertaken for furtherresearch. This is important in view of increasing mortality due tosuicide in India, which has increased by 43% in the last threedecades (Vijayakumar, 2010).

Due to reactivity of affect these patients’ severity of depressionmay be underestimated. They may be considered to have anxietydisorders due to their increased appetite and interpersonalsensitivities. The suicide risk in these patients may thus getundermined and they may receive sub-therapeutic doses of anti-depressants.

In summary, the authors would like to consider depression withatypical features as one large group of depressed patients, whichshould be carefully assessed for co-morbidities. Such depressionwith co-morbid anxiety and somatoform disorders form one sub-group, the other sub-group has co-morbidity with bipolarspectrum disorder and lastly the sub-group of ‘purely’ atypicaldepression. The relatively small sample size is a limitation of thisstudy.

Future research on longitudinal long term follow up of thesepatients will conclude on outcome of depression with and withoutatypical features and need for differential treatment approaches.Glimpses of our follow up patients have suggested that depressionwith atypical features is an unstable diagnosis over a period oftime. Some of these study patients subsequently developedpsychotic features; some changed diagnosis to schizoaffectivedisorder or developed a manic episode. In the absence of well-documented statistics and high attrition rate, we cannot includethis important finding as one of the conclusions.

5. Conclusion

Presence of atypical features is common in Indian patients withmajor depressive disorder. The diagnosis and severity of majordepression should not be missed despite preserved moodreactivity and not so deteriorated functioning. Severity of disorderand impairment of functioning caused is same despite presence orabsence of atypical features.

Presence of atypical features was often associated with co-morbid bipolar spectrum disorders, anxiety disorder and somato-form pain disorder. Higher level of impulsiveness especially motor

impulsiveness was associated with the presence of atypicalfeatures. Past history of suicide attempts and suicide ideationwas present and equal in either group.

Assessing for the presence of atypical features and associatedco-morbidities need not be a theoretical exercise, but rather aroutine clinical practice of a psychiatrist. This will aid in preciseand adequate management of this common disabling andpotentially fatal disorder.

Authors’ contribution

SD contributed toward planning of research study, literaturesearch, preparing protocol and determining method, data collec-tion, data entry, writing of manuscript; PP was responsible for datacollection, data entry, literature search, and assisted in writing themanuscript and tables; BK did data collection, data entry, literaturesearch; MG rendered the administrative help, acted as guarantor,and reviewed the final draft of the manuscript.

Funding

This study received funds from Maharashtra University ofHealth Sciences, Nashik, Maharashtra, India under Teachers’fellowship grant.

Conflict of interest

None.

Acknowledgement

We sincerely acknowledge help of senior statistician Dr SanjeevSarmukaddam in statistical analysis of the data.

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Dr Sharmishtha Deshpande, MD, works as a professor in the psychiatry department ofSmt. Kashibai Navale Medical College, Pune. She has over 12 years of teaching andresearch experience. She has presented and published research in psychiatry and inliaison with departments of paediatrics, dermatology and community medicine. She isalso interested in cultural and community psychiatry and has played a pivotal role in acouple of such research projects.

Dr. Poonam Patil, MBBS, DPM, from KEM Hospital, Pune. She has teaching and clinicalexperience of over six years and presently working as a senior resident in departmentof psychiatry at Smt. Kashibai Navale Medical College & General Hospital, Pune, for thelast two years. Her areas of interest are general psychiatry and child psychiatry.

Dr. Bhalchandra Kalmegh, MBBS, DPM, MD (USAIM), from Mumbai. He has over sixyears of clinical experience in Psychiatry and is working as a senior resident in thedepartment of Psychiatry at Smt. Kashibai Navale Medical College & General Hospital,Pune, for the last three years. His areas of interest are deaddiction & general psychiatry.

Dr. Madhav Ghate, MBBS and MD (psychiatry), from B J Medical College, Pune, DPMfrom CPS, Mumbai. He has 28 years of teaching experience in undergraduate andpostgraduate psychiatry. He is working with the National Chemical Laboratory, Puneon the research projects concerned with omega-3 fatty acids and mental health. Twopapers on these topics were published in international journals. He is at presentworking as professor and head, department of psychiatry, S K N Medical College, Pune.