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Subtypes of depression

Tanvir Singh, MD
Alina Rais, MD
Dept. Psychiatry,
University of Toledo Medical Center, Toledo, Ohio, USA

Objective

One of the major challenges in treatment of depression seems to be the heterogeneity of the disorder. It is not uncommon to see significant differences in symptomatic presentation of depress patients (1). Besides there are differences in age of onset, severity of course, treatment response and comorbid conditions. One assumption is that the heterogeneity is simply because there are different subtypes of depression (1). Main objective of this article is to look into the unique characteristics of some of the subtypes of depression, and their clinical relevance in overall recognition as well treatment of the depression.

DSM IV TR Classification of depression

DSMIV TR (2) has divided depression into two major classifications. One is bipolar depression, which could be bipolar 1 depression (history of mania), or bipolar II depression (history of hypomania), or cyclothymic depression (alternating hypomanic and brief depressive episodes).Other is unipolar depression which is major depressive episode (without any history of hypomania or mania) or dysthymia in which patients have two years (one in children and adolescents) of depressive symptoms without ever meeting the criteria of major depressive episode. DSM IV TR has also enlisted cross sectional specifiers of major depressive episode(catatonia, melancholic, atypical, postpartum),and longitudinal specifiers (chronic, seasonal, rapidly cycling).Depression has also been graded by DSM IV TR on the basis of severity of episode(mild, moderate, severe, psychotic).Besides DSM IV TR classification, some subtypes of depression like depression with anger episodes or agitated depression(3)have been identified in clinical practice and also studied in research settings.

Atypical depression

Key features are reverse vegetative symptoms (increase sleep and appetite), presence of mood reactivity, leaden paralysis (heavy (tired) feeling in limbs), and interpersonal rejection sensitivity (2).
Diagnostic validity of atypical depression was based on better response to MAO inhibitors and latent class analysis (class defined by reverse vegetative symptoms of hypersomnia and overeating) (4-6). Atypical depression when compared to other subtypes has been found to have relatively early age of onset, is more common in females, has higher axis I comorbidity, and is more commonly accompanied by family history of bipolar disorder. (4-6). Atypical depression is also unique variant of depression which has personality trait, “rejection sensitivity,’ as part of its diagnostic criteria.
Atypical depression with its chronic course, pattern of long standing emotional problems related to ‘rejection sensitivity,’ make it likely to be considered as just ‘personality disorder’ or simply ‘neuroses.
Fatigue being one of the prominent symptoms in atypical depressives can also result in misdiagnosis of chronic fatigue syndrome. That is why patients with no physical signs and symptom (like tender lymph nodes, sore throat) but with history of long standing fatigue should be carefully screened for presence of atypical depression. Atypical depression when diagnosed correctly has been found to respond well to treatment. Most of studies support good response to antidepressants in atypical depression (7-9). Though there do not appear to be any large scale studies which endorse the use of SSRI’s over MAOI,s as first line treatment of atypical depression, the potential for serious adverse effects with MAOI’s(hypertensive crisis) makes SSRIs an attractive and relatively safe first option.

Bipolarity-
1) Atypical depressive symptoms raise the suspicion of bipolar disorder (especially bipolar II) but they are not absolute markers of bipolar depression (4-6).

Points to remember
(1)Presence of ‘interpersonal rejection sensitivity’ can mislead to axis II diagnosis as the primary diagnosis. Such misdiagnosis would support decision unfavorable to trial of antidepressant which have been proven to be very effective in atypical depression.
(2)Early age of onset and presence of hypersomnia and hyperphagia can be considered as “just adolescent behavior”
(3)Symptom of ‘leaden paralysis’ can be misdiagnosed as ‘chronic fatigue syndrome’
(4)Patients with atypical depression exhibit ‘mood reactivity’. But presence of ‘mood reactivity’ is not suggestive of milder form of depression. Atypical depression carry high suicide risk as well risk of chronicity of symptoms (10).
(5)Symptoms of increased appetite and sleep in atypical depression can result in obesity.
(6)MAO inhibitors should be considered in patients who are resistant to trial of SSRI and other newer antidepressants

Melancholic depression

Key features are loss of pleasure, lack of mood reactivity, psychomotor change, and anorexia (2). Psychosis is common.
Melancholic depression is more common in older age and often present as depression with psychotic symptoms (11-12). Core symptom of melancholic depression is usually ‘psychomotor change’ (13). Melancholic depression in elderly mostly present with psychomotor retardation though psychomotor agitation is more common in younger patients. Patients suffering from melancholic depression endorse symptom of profound anergia along with very depress mood, worse in morning. Symptoms of melancholic depression seem severe enough to require hospitalization. Early morning awakening and loss of appetite are less common in younger patients (11-12). Many times it is labeled as part of dementia in the elderly (14). But sometimes melancholic symptoms of depression (structural melancholia) are present along with dementia (especially vascular dementia) (15-16).
Antidepressants from any class could be effective (17). Mirtazapine can be especially useful to counter severe anorexia (18). In some cases because of accompanying psychotic symptoms adjuvant antipsychotic medication are also needed. Dose of psychotropic’s need to be carefully regulated in elderly patients especially with accompanying dementia as they can easily go into delirium (15-16). ECT can be useful alternative and in severe cases even first line of treatment.
Bipolarity
Melancholic depression has been found to be common in bipolar I depression and relatively more frequently seen in inpatient setting (rather than outpatient) (19).Melancholic depression when part of bipolar II depression is more commonly associated with psychomotor agitatation (20).

Points to remember
(1)Melancholic depression in elderly can be easily mistaken as ‘just’ part of dementia.
(2)Both dementia and melancholic depression are often present in same patient.
(3)More common association with bipolar I disorder makes melancholic depression more vulnerable to adverse affects of monotherapy of antidepressants and it is even more vital to thoroughly screen for bipolar disorder.
(3)Neuroimaging can be helpful especially to differentiate conditions like vascular dementia.
(4)Melancholic depression does not always present as psychomotor retardation (younger people have psychomotor agitation)
(5)Psychosis is relatively more common than any other form of depression and use of atypical antipsychotic is warranted in most cases of accompanied psychosis irrespective of being unipolar or bipolar depression.
(7)Too aggressive use of psychotropic’s can result in delirium especially if there is comorbid dementia.
(8) ECT should be considered as an early option.

Vignette 1

Mr. J a previously healthy 69 year old retired cop, presented with conspicuous change in his personality. Mr. J who was always a confident, well respected, fearless man; became insecure, constantly seeking reassurance from his family about everything. No medical consultation was sought for this change in behavior. But six months later Mr. J seem to have depressed mood, loss of appetite, insomnia, significant psychomotor retardation. Family decided to seek psychiatric consultation. Mr. J was diagnosed with depression and started on Celexa 20 mg daily. A week later Mr. J had sudden episode of paresis of his left lower extremity. When taken to ER, it was found that Mr. J had stroke involving right parietal lobe. Week after discharge from hospital, Mr. J reported both auditory as well visual hallucinations along with worsening depression. Family described him as someone with no energy, unable to enjoy anything; poor sleep and even worse appetite. Mr. J also admitted to suicidal thoughts with plan to shoot him. He was admitted to inpatient psychiatric unit and Celexa was switched to Mirtazapine. Treatment team was concerned about Mr. J suicidal thoughts and decided to treat him aggressively. Mirtazapine was started on 15 mg and increased to 30 mg hs next day. Risperidone was started at 2 mg and increased to 4 mg hs the next day. Day after increase in dose of Resperidone and mirtazapine Mr. J started oscillating between somnolence and agitation. It seemed that patient had gone into delirium with sudden increase in dose of psychotropics. Risperidone was reduced to 1mg hs. Mr. J responded well to reduction in dose of Risperidone and seemed to have much clear sensorium. Reported no psychotic symptoms. Mirtazapine was maintained at 30 mg hs. Neuro psych testing was ordered. Mr. J showed significant cognitive deficits during neuropsych testing. Magnetic resonance showed multiple infarcts. Impression was that Mr. J has vascular dementia along with melancholic psychotic depression. Mr. J was discharged home and a month later while on Resperidone 1 mg hs and mirtazapine 30 mg, continue to report improvement in mood as well other symptoms of melancholia.
Discussion- Like in above case melancholic depression can occur along with dementia (vascular in above case) though it is hard to predict as to what happened first. Psychosis is relatively common. Elderly people who also have comorbid dementia (cognitive deficits) are much more prone to complications from over aggressive use of psychotropics.

Seasonal affective disorder (SAD)

Key feature is the temporal relationship of depressive symptoms with specific times and seasons of the year (2).
As per DSM IV seasonal affective disorder is a specifier for major depressive episode or depressive disorders. The season of onset is usually autumn and winter and remission usually occur in spring and summer. But some patients have what is termed reverse SAD, and experience depressive symptoms in spring and summer. In summer, some patients can even have hypomanic symptoms or episode. Much like atypical depression it is more common in females and younger people (21).
Symptoms of depression can be different based on winter or summer SAD. Summer SAD usually have insomnia, irritability, weight loss, decreased appetite and increased libido as prominent symptoms while winter SAD have loss of energy, social withdrawal and increased sleep and appetite. Winter SAD which is more common variant sometimes present as low energy or ‘feeling of being constantly tired’ as the only complaint. And similar to atypical depression can be misdiagnosed as chronic fatigue syndrome. Seasonal affective disorders are relatively more common in areas with cold and long winters (22). Phototherapy (light therapy) as well antidepressants and psychotherapy can be effective for treatment of depressive symptoms (23-24). Amongst antidepressants though SSRI’s, venlefaxine, bupropion have all been found effective, it is Wellbutrin XL which is FDA approved for seasonal depression.(25)Due to lack of any large scale comparative study it is difficult to say as which treatment(light therapy, psychotherapy, medications) is more effective than other(26-27).

Bipolarity
Unclear if it is more common in bipolar or unipolar depression. SAD when part of bipolar disorder is more common in bipolar II than bipolar I depression (21).

Points to remember
(1)Seasonal affective disorder can be both winter as well summer type.
(2)Patients coming with mood symptoms should always be screened for any seasonal variation in their symptoms.
(3)Diagnosis can be often mistaken for atypical depression or bipolar depression (because of seasonal mood variation).
(4)Seasonal affective disorder is not a milder form of depression. Suicide risk requiring hospitalization is possible.
(5) Treatment is unique as Phototherapy can be equally effective.
(6) Eating disorders and ADHD are frequently comorbid (27).

Dysthymic disorder

Key features are presence of persistent depressive symptoms for one year in children or adolescents and two years for adults. Prominent symptoms can be depress mood, low energy, low self esteem, feeling of hopelessness (2)
In dysthymia, vegetative symptoms of depression like sleep and appetite disturbance are less common. As per diagnostic criteria, there should be no history of hypomania, mania or mixed state. Interestingly though studies suggest that almost one third of patients with dysthymia can switch to hypomania when on antidepressants (28-29). Dysthymic disorder is considered by many as relatively low grade depression. But almost two third of individuals with dysthymia eventually have a major depressive episode (28-30). Many times patients of dysthymia experience sufficient symptoms to meet the criteria of major depression but since they experience them in such a sporadic way, never could have met criteria of major depression. Like any other form of chronic depression, dysthymia carry high risk of relapse.
Regarding treatment, all types of treatment (psychotherapy, psychopharmacology) which are effective for any other depressive disorders are effective for dysthymia. But being a chronic condition with high risk of relapse, treatment for dysthymia needs to be more aggressive. Risk of relapse with early termination of treatment can be high. Effective treatment for dysthymia usually require relatively higher dose of antidepressants (31). Even in psychotherapy, patient with dysthymia need more frequent therapy sessions (32). Cognitive behavioral analysis system of Psychotherapy, Cognitive behavior therapy, interpersonal psychotherapy, have all been studied with positive results (32-34).

Bipolarity

Part of unipolar depression but switch episodes of ‘hypomania’ with antidepressants possible
Points to remember
(1)Dysthymia is mistaken for just ‘minor depression’ or its symptoms are ignored as just part of ‘depressive personality’. Fact is that dysthymia is chronic form of depression with high risk or relapse and needs to be recognized promptly and managed effectively.

Agitated/hostile depression or Depression with anger attacks

Key symptoms can be persistent irritable mood, ‘anger problems’ which could be severe enough to result in violent outbursts (3).
This subtype of depression though not part of DSM has been extensively discussed in literature as well studied in research. Agitated or hostile depression has also been described as subtype of depression seen in people who ‘snap easily’ and admits to ‘temper problems’ as their main concerns. Hostile depression contradicts the traditional psychodynamic concept of depression (anger directed inwards or inability to direct anger outwards).
Irritable mood is considered as mood with strong feeling of unhappiness with behavioral or verbal outbursts which could be unprovoked or disproportionate to the trigger. Agitated depression has gained attention after several studies done on subjects with ‘anger problems’ and ‘irritable mood’ showed a strong link with history of depression (35-39). Patients with this subtype of depression can suffer significant impact on their social and occupational aspects of life, specifically because of their temper problems. Patients with hostile depression are often mistaken for antisocial personality disorder or impulse control disorder. Correct diagnosis in such cases is vital as treatment of depression rather than just ‘anger’ is important. Even this subtype of depression has been seen to respond well to trial of antidepressants (35, 37).
Bipolarity
Can be part of both bipolar or unipolar (39)

Points to remember
(1)Agitated depression is often considered as an ‘Anger problem’ But ‘anger’ is just prominent symptom of underlying depression and ‘anger management’ as the only intervention is not adequate.
(2)Depression with irritable mood and anger problems does not necessarily mean bipolar disorder. It could well be unipolar depression.

Vignette 2

Mr. B was 32 year old man referred by his therapist for psychiatric evaluation. Mr. B was mandated ‘anger management’ by the court after being charged with domestic violence. He had a long history of anger problems and during one of the episodes threatened to hit his spouse with chair who called the police. Therapist reported that Mr. B has been very compliant with treatment and has made a serious effort to improve his temper. But he continues to suffer from spontaneous episodes of irritable mood. When interviewed Mr. B endorsed long term history of irritable mood, psychomotor agitation, trouble with sleep, poor concentration. Mr. B admitted to feeling guilty after each outburst and ruminating about it for long time. Denied any manic/hypomanic episode or any psychotic symptoms. Mr. B said that his Primary care physician tried him on Depakote and Trileptal with no positive effect. After thorough evaluation Mr. B was diagnosed with Depression with anger attacks (depressive disorder NOS) and started on Selective Serotonin Reuptake Inhibitors (SSRI). Mr. B responded well to trial of antidepressant Celexa and reported significant improvement in his irritability and temper outbursts.
Discussion- Irritable mood, anger directed outwards could be part of agitated/hostile depression (also termed depression with anger attacks). In such cases anger is the most prominent symptom of underlying depression. Effective treatment is not possible unless underlying depression is treated.

Differentiating bipolar and unipolar depression

Universally accepted is the importance of differentiating bipolar and unipolar depression. National Manic Depressive association (NMDA) in a recent survey found 69% of patients with bipolar disorder were initially misdiagnosed, with more than one third of cases remaining misdiagnosed for more than ten years(40-41). DSM IV TR has the same clinical criteria for major depressive episode in both unipolar or bipolar depression. But there are significant differences in their effective treatment. Treatment based on misdiagnosis can prove detrimental in worsening the course of illness (40-42). Antidepressant monotherapy in bipolar depression can result in serious complications of ‘episodes of mood switch’ or even ‘rapid cycling’. Though none of subtypes of depression serve as diagnostic marker for bipolar disorder. But never the less recognition of certain subtypes like atypical or melancholic depression especially when combined with positive family history of bipolar disorder or multiple failed trials of antidepressants (40-42), is helpful in raising the suspicion of bipolar disorder. This awareness can be vital especially in primary care setting to get appropriate referral for more comprehensive screening and to avoid misdiagnosis.

Vignette 3
Ms A, who is a 32 year old obese woman presented to her new primary care physician for regular medical checkup. Her main concern was the chronic depression. Ms A reported being moody and depressed since her teenage years. Ms A said that it all started when she was dumped by her boyfriend. Ms A said that her previous primary care physician had tried Fluoxetine, Sertraline and Wellbutrin with no benefit from any of them. Ms A reported feeling lethargic, with hypersomnia and hyperphagia. Ms A seemed very distressed and reported that she recently lost her fifth job because of her mood problems.
Discussion-Symptoms of atypical depression and history of failed trials of antidepressants raise the suspicion of bipolar depression for the PCP. And since unlike the previous PCP Ms a new physician was more aware, she was referred for formal psychiatric evaluation.
And with more careful and thorough history during psychiatric evaluation, Ms A revealed episode lasting 1-4 days when she would feel elated. Ms A said that she never thought of these episodes as suggestive of mood switch, for her it was time when she try to get everything done. She hardly slept during those days but remained energetic. Ms A was diagnosed with bipolar disorder type II started on Lamotrigine.
Ms A responded well to trial of Lamotrigine and two months later reported feeling ‘normal’ for the first time.

Discussion

We have made significant improvements in the treatment of depression and mood disorders in general. However the effective treatment options can only be utilized if we can make the correct diagnosis and reach the maximum people who are suffering from depression.
Diagnostic criteria for depression are based, largely on the consensus position among experts, rather than by objective markers. But the variability in presentation of depressive symptoms can easily result in missed diagnosis. It has been seen that individuals who present with unique symptoms or characteristics of subtypes of depression rather than classical symptoms of major depression are viewed characteriological or just ‘neurotic’ and never treated effectively. Unfortunately missed or misdiagnosis in such cases result in denial of interventions which could have been effective in managing their depression. Moreover recognition of subtypes of depression is extremely helpful in predicting course of illness, possible complications, and even bipolarity in some case. Proper recognition of subtypes can be so helpful in formulating more effective treatment plan. For example one would not choose phototherapy as treatment option in patient with seasonal affective disorder, MAO inhibitor in atypical depression after failed trial of SSRI, or order neuroimaging in elderly depressed melancholic patient unless aware of distinct subtypes of depression and their unique characteristics. Fact that all the prominent subtypes of depression if recognized properly responds well to treatment makes it even more imperative that they are properly identified.
Conclusion- To conclude inspite of all the controversy about week diagnostic stability in depression subtypes, they are vital in improving the recognition of clinical depression and thus formulating the right treatment approach. Subtypes of depression and their many distinct clinical presentations need to be recognized even at primary care setting. Need of the time is well defined symptom profile for each subtype of depression which is universally accepted.

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First published December 2007