DEPRESSION: AN OVERVIEW

FROM HISTORICAL ASPECTS TO CURRENT DAY PRACTICES

Introduction

 WHO defines health as a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.¹ It implies the need of taking care of mental health needs to build a healthy globe. A recent meta-analysis estimated that the prevalence of mental health disorders stood at 22.1%.² Depression is a common mental health disorder that limits socio occupational functioning and decreasing quality of life. India is home to an estimated 57 million (18% of global burden) people affected by depression.³ Depression is characterized by pervasive sadness, easy fatiguability, loss of interest in pleasurable activities, feeling guilty, hopelessness, disturbed sleep & appetite, suicidal behaviour, and impaired socio-occupational functioning. it is currently the third most leading cause for ‘years lived with disability’ (YLD) in both men and women world-wide and estimated to be the first most leading cause by 2030.⁴ It is also contributing 10% of total ‘disability adjusted life years’ (DALYs) world-wide.⁵ Prevention strategies have been shown to reduce the burden of depression, and there are effective treatments. In this paper we will have an overview of depression from historical aspects to current day practices.

The History

History is a screen through which the past enlightens the present, and the present brightens the future. Depression is often presented as a fashionable disease, considered to be the disease of 21^st century. Yet it has already been described in history through the ages. The earliest written accounts of what is known as depression appeared in ancient Mesopotamian texts in the second millennium BC, discussed it as a spiritual rather than a physical condition.

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The period between 500 BC and 500 AD is considered the age of rationalism. Greek physician, Hippocrates, (460 BC – 370 BC) is considered the first physicist who describes melancholy or depression clinically. He defines it as ‘if fear and sadness last for a long time, such a state is melancholy’. He suggested the imbalance of four body humors as the cause rather than the spiritual causes such as demonic invasions.⁶ Another Greek physicist, Galen, (129 AD – 216 AD) further devised a comprehensive typology of temperaments, sanguine, choleric, melancholic, and phlegmatic based on humoral theory.⁷ They speculated that excess of black bile causes melancholic temperament.

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Bloodletting was a way to restore humor in depressed patients.⁸ From the 4^th century AD, during the middle age, religion overtakes scientific interest and medical research. During this period many primitive methods of treatment for depression continued to be the norm, such as starvation, shackles, and beating of mentally ill. The period of Renaissance, during the 16^th and 17^th century, is restored the previous reasonings of physiology behind melancholy. Even a clergyman, named Robert Burton, wrote and published ‘the anatomy of melancholy’, asserted that depression had specific causes like poverty, fear, isolation.⁹ Practiced treatment strategies were music, exercise, herbal medicine, marriage, and bloodletting. During the 18^th and 19^th centuries, the age of enlightenment, the views on melancholy took a rather grim turn. It came to be viewed as a weakness in temperament, that was inherited and could not be changed. The result was that people were shunned or locked up. In the later part of 19^th century, medical communities tried varies treatment strategies like lobotomies, spinning stools, immersion therapy, and electroshock therapy.

The Contemporary Era

 The modern concept of depression arose from earlier diagnostic formulations of melancholia. The term depression began to appear in literature in 19^th century.¹⁰ In 1895, a German psychiatrist, Emil Kraepelin,  simplified the work of his predecessors and delineate the foundations of the modern classification of psychiatric disorders. He distinguished manic- depression (now known as bipolar disorder), as an illness separate from dementia praecox (now known as schizophrenia).¹¹ In his ‘introduction to clinical psychiatry’(1907) he carried out a

varied classification of depressive states, such as melancholy, depressive circular states, catatonic stupor, manic depressive mixed states, catatonic excitation etc. Around the same time, psychodynamic theory and psychoanalysis were developed. Sigmund Freud developed talking therapy based on his psychoanalytic explanation for depression.¹² The behavioural psychologist’s behavioural explanations, Aaron Beck’s cognitive explanations, Martin Seligman’s learned helplessness theory were paved path for cognitive behavioural therapy for depression around the same time.¹³ Even during this time, however, other doctors saw depression as a brain disorder. In the latter part, the approaches increasingly stressed the biopsychosocial model that looks at biological, psychological, and social factors. Most recently ‘The medical model of mental disorders’ emerged and suggested that mental disorders primarily caused by biological/physiological factors and can be treated with medication. Biological explanation of depression focuses on genetics, brain chemistry, anatomy, and hormones, thus leading to development of anti-depressants.

The Medical Model of Depression

1. The most widely applied ‘biogenic amine hypotheses’ proposed in 1960s and 70s suggested that impairment or dysregulation as the mechanism behind depression. This theory explains phenomenology and opposite episodes, suggests treatment.¹⁴ Neuro endocrine theories suggested the disinhibition of the hypothalamic-pituitary-adrenal axis, characterized by steroidal over production, and explains anxious depression. Based on this theory, the dexamethasone suppression test (DST), clonidine, thyrotropin challenge data, in aggregate identify most persons with clinical depression; argues that clinical depression is a legitimate disease.¹⁴ Neuro physiological theory suggests that electrophysiological disturbances leading to neuronal hyperexcitability/kindling as the mechanism behind depression. It explains the phenomenology and recurrence.¹⁴ William McKinney and Hagop Akiskal developed a concept that considers depression as the final common pathway of various psychological and biological processes. Based on this an integrative pathogenetic model was developed including developmental predispositions, heredity, gender, and limbic diencephalic dysfunction.¹⁴ 

The Classification

The two official classificatory systems currently in practice are Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and International

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Classification of Diseases (ICD-10). Until DSM-2 diagnostic criteria were much dependent on psychoanalytic and Myrian concepts of reaction types. Structured criteria were used in DSM-3 and successors.¹⁵ DSM- 5 sub-categorized depression into major depressive disorder (MDD), persistent depressive disorder (Dysthymia), premenstrual dysphoric disorder, and a new entity disruptive mood dysregulation disorder (DMDD). The specifiers include single/recurrent episodes, mild/moderate/severe forms, with psychotic features, in partial/full remission.¹⁶ (see table 1). ICD-10 represented major advances over their predecessors till ICD-9 and sub-categorized into depressive disorder, recurrent depressive disorder, and persistent depressive disorder include cyclothymia and dysthymia. ICD-10 have both major and minor criteria for diagnosis of depression and sub-divided into mild, moderate, and severe forms with or without psychosis.¹⁷

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Treatment

Until the 20^th century treatments for major depression generally weren’t enough to help patients. The use of lobotomies, bloodletting, immersion therapies, spinning stools in desperation could only prove barbaric methods without relief. The introduction of talking therapy by Freud, cognitive behavioural therapy by Beck had happened in first half of 20^th century. Electro Convulsive Therapy (ECT) was also sometimes used for depression. The decade of 1950s was an important period, which heralded the drug therapy for treatment for depression, where previous treatments only focused on psychotherapy. The accidental discovery of Isoniazid being useful for depression, leads to the invention of Imipramine and other Tricyclic Antidepressants (TCAs). To reduce side effect profile of TCAs, further emerged Fluoxetine (1987), Sertraline (1991), Paroxetine (1992), Fluvoxamine (1994), Citalopram (1998), and Escitalopram (2002) which were grouped as Selective Serotonin Reuptake Inhibitors (SSRIs). The emergence of SSRIs revolutionized treatment of depression with being occupied more than 50% share of current day antidepressant use. They are found to be safe and effective throughout the period. Further approved antidepressants like Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) like Venlafaxine, Desvenlafaxine, Duloxetine, Bupropion, and Mirtazapine have almost similar safety and effectiveness profile with SSRIs.^18,19 More recently approved antidepressants are Vortioxetine, and Vilazodone, which are showing promising side effect profile over previous ones.^20,21 The promising results on antidepressant safety and efficacy profiles were established with major studies include STAR*D and STEP-BD.²²

Newer Treatments

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 Despite the current day widely practicing pharmacotherapy, and psychotherapy, the need of newer treatment options is still there in the management of depression, Owing to the facts that relapses, resistance to medication, and compliance issues. Non-Invasive Brain Stimulation (NIBS) techniques open new horizons in the management of this disorder. Repetitive Transcranial Magnetic Stimulation (rTMS), Transcranial Direct Current Stimulation (TDCS), Transcranial Electrical Stimulation (TES) are such techniques. rTMS showed effectiveness in treatment of unipolar depression in many studies, and in bipolar depression.²³ The recently emerged deep RTMS with H coils further enhanced the clinical outcomes because of its deeper and broader neuronal activation. TDCS also found as effective in treatment of depression, in a recent RCT conducted by Naeim et al.²⁴ US-FDA recently approved rTMS for major depressive disorder, obsessive compulsive disorder.²⁵ Biofeedback is another newer treatment option available as an adjunct to management of depression. A randomized trial found biofeedback as an effective tool and alternative form of management in reducing depression.²⁶ Invasive brain stimulation techniques such as, Deep Brain Stimulation (DBS), Vagus Nerve Stimulation (VNS) are also in consideration and under research, with limited literature available to date.

Conclusion

 Depression is a common mental health disorder with significant burden world-wide. The current understanding of etiology of depression develops over centuries, from Hippocrates to the current day medical model of depression, but complex than what we yet understand. Symptoms and diagnostic criteria were becoming structured over the course and in the process of standardization. Management options available are increasing by the period, now stands at pharmacotherapy, psychotherapy, brain stimulation techniques both invasive and non-invasive, and other alternate therapies such as biofeedback. Recent FDA approval of rTMS in management of depression opens the new horizon for effective treatment and needs to be embraced. As the available data on these newer treatment techniques is promising but limited, further research with tighter study designs is the need of the hour. An integrative treatment approach in management of depression would be beneficiary.

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Author: Dr. Balaji Sainath, Consultant Psychiatrist, ANC – Gachibowli.