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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 47-57

Pittaja Unmada: Hyperthyroidism with mania?/Psychotic or irritable mania?


Department of Kaya Chikitsa, SKS Ayurvedic Medical College and Hospital, Mathura, Uttar Pradesh, India

Date of Submission04-Dec-2019
Date of Acceptance16-May-2020
Date of Web Publication21-Aug-2020

Correspondence Address:
Dr. Prasad Mamidi
Department of Kaya Chikitsa, SKS Ayurvedic Medical College and Hospital, Mathura, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijny.ijoyppp_19_19

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  Abstract 


Bhuta vidya” (Ayurvedic psychiatry) is one of the eight branches of Ayurveda (an Indian system of medicine) and it deals with the management of various psychiatric disorders. Unmada (a psychiatric disorder) is characterized by deranged mental functions and it is classified into five types (vataja, pittaja, kaphaja, sannipataja, and agantuja). “Pittaja Unmada” (PU) is one of the five types of unmada described in all major Ayurvedic texts and it comes under “Doshaja Unmada” (psychiatric disorder which occurs due to the aggravation of doshas) category. Scientific literature on PU is scarce and the present study is focused to explore this condition. The etiopathology of PU seems to induce systemic inflammatory sequelae and also autoimmune reactions which again may lead to the manifestation of autoimmune thyroid disease or Graves' disease (GD). Signs and symptoms of PU can be classified into two groups, psychological and physiological. The psychological and physiological features of PU have shown similarity with conditions like manic episode, bipolar disorder (BD), GD, thyrotoxicosis and hyperthyroidism. PU is similar to “psychotic mania” or “mood disorder with psychotic features” or “manic episode due to general medical condition” or “BD comorbid with hyperthyroidism or GD”. PU or “bipolar affective disorder” can be managed successfully by “Virechana” followed by internal medicines.

Keywords: Bipolar disorder, Graves' disease, hyperthyroidism, mania, Pittaja Unmada, Unmada


How to cite this article:
Mamidi P, Gupta K. Pittaja Unmada: Hyperthyroidism with mania?/Psychotic or irritable mania?. Int J Yoga - Philosop Psychol Parapsychol 2020;8:47-57

How to cite this URL:
Mamidi P, Gupta K. Pittaja Unmada: Hyperthyroidism with mania?/Psychotic or irritable mania?. Int J Yoga - Philosop Psychol Parapsychol [serial online] 2020 [cited 2020 Sep 29];8:47-57. Available from: http://www.ijoyppp.org/text.asp?2020/8/2/47/292937




  Introduction Top


Bhuta vidya” (Ayurvedic psychiatry) is one of the eight branches of Ayurveda (Indian system of medicine), which deals with the management of various psychiatric conditions. Unmada (a psychiatric disease) is mentioned in all classical texts of Ayurveda and it is characterized by the derangement of manas (mind), buddhi (cognitive functions), samgna gnaana (orientation), smriti (memory), bhakti (interests), sheela (character/personality), cheshta (psychomotor activity/behavior), and achaara (conduct).[1]Acharya Charaka” has mentioned five types of Unmada (vataja, pittaja, kaphaja, sannipataja, and agantuja).[2],[3] In “Sushruta samhita,”[4]Ashtanga samgraha,”[5]Ashtanga hridaya,”[6]Madhava nidana,[7] and “Bhava prakasha,”[8] six types of Unmada have been mentioned (vataja, pittaja, kaphaja, sannipataja, vishaja, and aadhija/manodukhaja) [Table 1].

Previous studies have compared “Kaphaja unmade” with “myxedema psychosis”[1] and “Grahonmada/bhutonmada's” with various neuropsychiatric conditions.[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22]Pittaja Unmada” (PU) was correlated with “bipolar affective disorder (BPAD)” in a case report.[23] Scientific literature on PU is scarce and the present study is focused to explore this condition. The present study has explored the similarity between PU and “psychotic or irritable mania” or “mania with hyperthyroidism” in the following sections.
Table 1: Classification of Unmada according to various Ayurvedic classical texts

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  Review Methodology Top


Ayurvedic literature regarding “PU” has been collected from major Ayurvedic texts (Charaka samhita, Sushruta samhita, Ashtanga sangraha, Ashtanga hridaya, Madhava nidaana, Bhava prakasha, and Bhela samhita) including their commentaries. Electronic databases such as “Google Scholar “ and “Google Search” were searched for relevant studies and reviews published till November 2019, irrespective of their appearance/publication year. The keywords used for search were, “Pittaja Unmada,” “Unmada,” “Bhutonmada,” “Grahonmada,” “Hyperthyroidism,” “Graves's disease,” “Hyperthyroidsim with mania,” “Graves ophthalmopathy,” “Bipolar disorder,” “Mania,” “Irritable mania,” “Psychotic mania,” “Mood disorder,” “Mood disorders with psychotic features,” “Schizophrenia,” and “Bipolar affective disorder.” Abstracts as well as full-text articles which are open access and in English language were only included. Relevant Ayurvedic material collected from the textbooks available at “Abhilashi university library” has been referred.


  Exploration of Pittaja Unmada Top


Ayurveda has proposed three dynamic doshas (pathophysiological entities), as the basis of all bodily functions. The three doshas are termed as Vata, Pitta, and Kapha. The “Pitta dosha” (one of the three pathophysiological entities) is responsible for transformative processes such as digestion, metabolism, energy production, and maintenance of immunity. At the cellular level, Pitta dosha is responsible for action of enzymes, growth factors, hormones, energy homeostasis, and maintenance of basal metabolism. Imbalance or disturbed interactions between doshas is considered as a major cause of disease. Inflammatory diseases are associated with vitiation of Pitta dosha.[24]

Unmada is a major psychiatric illness described in all Ayurvedic classics and it is characterized by deranged mental functions. Unmada is caused by the vitiation of shareera and manasika doshas. Detailed description of Unmada is available in all major Ayurvedic texts. Differences in opinion are visible regarding classification of Unmada among different texts [Table 1]. PU is mentioned and described by all major Ayurvedic texts and it is classified under “Doshaja Unmada” (psychiatric disorder which occurs due to the aggravation of somatic pathophysiological entities). “Pitta” gets aggravated by various etiological factors, afflicts the heart of a patient, and leads to a serious type of “Unmada” instantaneously termed as “PU.”[2],[3]


  Etiopathogenesis of Pittaja Unmada Top


According to Charaka samhita (an ayurvedic textbook of medicine written by Agnivesha), various etiological factors such as indigestion, excessive intake of pungent, sour, hot food items, and intake of vidahi (which cause burning sensation in stomach) type of foods cause accumulation and aggravation of “pitta dosha.” The aggravated pitta spreads and afflicts the heart of a patient who does not have self-control and produce a severe psychiatric condition immediately.[3] Aggravated doshas spreads upward and occupies the channels of the upper parts of the body (head or heart) and produce unmada. There is no specific etiology mentioned for PU in Sushruta samhita (an ayurvedic textbook of surgery written by Sushruta).[4] Other texts also have expressed similar views.[5],[6],[7],[8]


  Signs and Symptoms of Pittaja Unmada Top


The signs and symptoms of PU according to Charaka samhita are “Amarsha” (intolerance/impatience), “Krodha” (anger), “Samrambha” (agitation/arrogance/boldness/harshness), “Abhihanana” (violence), “Abhidravana/Atidravana” (wandering/restlessness), “Pracchhaya sheetabhilasha” (seeking cold places and items), “Santaapa” (excessive body temperature), and “Taamra, harita, haridra and samrabdhaakshata” (copper colored, greenish, or yellowish eyes), “Vinagna bhava” (nudism), “Santarjana” (threatening/abusing), and “Rosha” (rage/furious).[2],[3] According to Sushruta samhita, “Trishna bahula” (excessive thirst), “Sweda bahula” (excessive sweating), “Daaha bahula” (excessive burning sensation), “Bahu bhuk” (voracious eating/excessive appetite), “Vinidra” (insomnia), “Jalaantara vihara sevi” (preferring cold places or water), and “Pashyati taaraka diva” (seeing stars in morning/visual hallucinations) are the signs and symptoms of PU [Table 2].[4] In Bhela samhita (an ayurvedic textbook of medicine written by Bhela), “Geetaani bhajate nityam” (always indulges in singing) is explained as a characteristic feature of PU.[25] The signs and symptoms explained in other Ayurvedic texts are similar to the description of Charaka and Sushruta samhitas' [Table 2].[5],[6],[7],[8]
Table 2: Pittaja Unmada lakshana's according to various Ayurvedic classical texts

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Signs and symptoms of PU can be divided into two groups based on their nature (psychological or physiological). Amarsha, Krodha, Samrambha, Abhihanana, Abhidravana, Atidravana, Vinagna bhava, Santarjana, Rosha, Vinidra, Pashyati taaraka diva, etc., come under the category of “psychological signs and symptoms,” whereas features such as Pracchhaya sheetabhilasha, Santaapa, Taamra, harita, haridra and samrabdhaakshata, Trishna bahula, Sweda bahula, Daaha bahula, Bahu bhuk, and Jalaantara vihara sevi come under “physiological signs and symptoms” of PU [Table 3]. The description of both psychological and physiological signs and symptoms of PU has been explored with contemporary psychiatric literature in the following sections.
Table 3: Similarity between “Pittaja Unmada” and “Psychotic/Irritable Mania” or “Mania with hyperthyroidism”

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  Psychological Signs and Symptoms of Pittaja Unmada Top


Amarsha (impatience/intolerance/irritability)

The word “Amarsha” means “intolerance” or “impatience” or “irritability.”[3],[7] The nature of manic symptoms is multidimensional. The factor analysis of manic symptoms has identified three clinically meaningful factors. These factors represent “elated mania,” “irritable mania,” and “psychotic mania.” The “irritable mania” is characterized by excessive irritability and increased motor activity or energy. Disruptive-aggressive behavior is also seen in irritable type of mania. The association of irritability with aggressive behavior has been found.[26] Impulsivity and labile mood are the features of “borderline personality disorder” and BD.[27] Psychomotor instability is found in BD and “attention deficit hyperactivity disorder” (ADHD).[28] Irritability must be present for the diagnosis of mania or hypomania.[29]Amarsha” explained in PU represents “labile mood” or “irritability” of mania.

Samrambha/Abhidravana/Atidravana (elated mood/grandiosity/agitation/wandering/restlessness/arrogance)

The word “Samrambha” means “excessive confidence” or “excessive boldness” or “heroism.”[3]Abhidravana” means “running” or “attacking” or “run up to or near”.[2]Atidravana” means “roaming restlessly” or “fast movements” or “wandering nature.”[3] BD is a complex disease with heterogeneous clinical presentations. Manic phases of BD are marked by irritability, exalted mood, and increased energy levels.[30] “Elated mania” is characterized by “elevated mood” or “euphoria” or “grandiosity.”[26] Increased motor activity not only was more important than changes in mood in characterizing mania but also represents the core feature of the syndrome. Among all six symptoms of mania, the item “increased energy” was the one that presented the highest factorial loading.[29] Acute agitation is a common presentation of a manic episode.[31] Increased risk-taking behavior, increased motor activity, and increased impulsivity are the important features comprising the clinical state of mania.[32]

Impulsiveness is a clinical feature of BD. Impulsivity refers to a predisposition toward unplanned reactions without consideration of consequences and can include risky decision-making, self-reported high-risk attitudes, poor response inhibition, and rapid decision-making. BD is often characterized by impulsive behavior and increased tendency to work toward a reward, often without sufficient planning. Bipolar patients consistently show abnormalities on measures of impulsivity and show deficits on behavioral tasks which require planning and forethought.[33] Mania is characterized by reckless behavior such as impulsive spending and sexual indiscretions.[34] Excessive confidence, increased energy, psychomotor agitation, and willingness to engage in reward-oriented behaviors without considering the potential negative consequences are the key features of mania.[35]

Delusions (or ideas) of grandeur (grandiosity) with markedly inflated self-esteem is found in mania. The person with mania is unusually alert, trying to do many things at one time. There is marked increase in activity with excessive planning and at times execution of multiple activities. The mood becomes expansive, which is unceasing and unselective enthusiasm for interacting with people and surrounding environment. The mood may become irritable, especially when the person is stopped from doing what he wants. There is an increased psychomotor activity ranging from over activeness and restlessness to manic excitement where the person is involved in ceaseless activity.[36]Samrambha” represents grandiosity or elated mood or impulsivity or increased energy levels of mania, whereas “Abhidravana” and “Atidravana” represent increased motor activity or agitation or psychomotor agitation or restlessness, etc., features seen in mania or BD.

Krodha/Taikshnya/Abhihanana/Santarjana/Rosha (anger/abusive/violent/aggressive behavior)

Signs and symptoms of PU such as “Krodha” (anger), “Taikshnya” (aggressiveness), “Abhihanana” (violence), “Santarjana” (threatening/abusing), and “Rosha” (excessive rage) represent excessive anger, aggressiveness, violent behavior, and reckless behavior, features commonly found in BD or mania. Criminal acts are common among patients with BD and are often associated with comorbid disorders, including substance use disorders, conduct disorders, ADHD, and personality disorders.[30] Violent behavior is relatively common in BD and usually occurs during acute manic episodes. Patients with acute mania often require hospitalization, as their symptoms (grandiosity, impulsiveness, agitation, and psychosis) may have substantial legal, penal, civil, work-related, and social repercussions. Manic patients display high levels of violence during the early weeks of hospitalization and exhibit violent behavior in the community in the 2 weeks prior to admission. Outbursts or aggressive states are associated with rapidly executed, impulsive acts of unexpected violence, occurring in response to minimal provocation or for no discernible reason. The tendency to engage in risky and aggressive behaviors is a core feature of the manic episodes of BD.[37]

Aggression is an overt action intended to harm others. Verbal aggression includes screams, abuse, or threats. Hostility denotes unfriendly attitudes. Overt irritability, anger, resentment, or verbal aggression is the manifestation of hostility. BD patients have shown significantly higher aggression scores than control groups. A study has revealed four subtypes of mania, one of them labeled as “aggressive”. Neuropsychological dysfunction, perhaps as a trait, is a predisposing factor for aggression in bipolar patients. These neuropsychological findings with the elevated trait hostility and impulsivity could be seen as a part of a diathesis that predisposes some bipolar patients to become aggressive when experiencing the stress of a manic episode.[31] Irritability and disruptive-aggressive behavior are the two features of “Young Mania Rating Scale”.[38],[39] Dysphoria denotes a condition of disagreeableness, nervous tension, hostile emotional reactivity, and propensity for aggressive acting out. BD and schizophrenia are the two major psychiatric illnesses that are likely to predispose to homicide.[40]

Studies have shown that traits related to emotional instability and hostility are elevated in bipolar spectrum disorders.[41] The irritability associated with mania has a much more hostile, vicious, and attacking in quality. Along with irritability, extremely impairing dysphoric and explosive episodes occur daily with little or no precipitant in adolescents with mania. These explosions may lead to destruction of property. Swearing and hostile comments are also common. Clinical presentations of adolescents with BD are variable, including disruptive behavior, moodiness, irritability, impulsivity, low frustration tolerance, and explosive anger.[42]

Geetaani bhajate nityam (fond of singing or music/euphoria)

Geetaani bhajate nityam” (always indulged in singing and other musical activities) is explained as a feature of PU in “Bhela samhita” only.[24] It is also one of the characteristic features of “Gandharva grahnomada” (GG). GG is correlated with a condition of BD associated with obsessive–compulsive disorder (OCD) or mania according to a previous study.[11] Novelty seeking is a personality trait found elevated in the patients of bipolar spectrum disorders.[41] Studies have provided consistent evidence for elevated rates of BD in samples of famous individuals. Creativity is particularly found among those with either mild forms of BD. Musicians have been shown to have higher scores on measures of manic and cyclothymic temperament. It is evident that many famous artists, musicians, and authors have gone through periods of manic symptoms, particularly when very mild manic symptoms are considered. Heightened impulsivity in BD promotes expressiveness without constraints and also openness to experience which may be the reason for heightened creativity. Positive emotional states broaden attention and thinking, widening the array of precepts, thoughts, and images that come into awareness. One of the common symptoms of manic episodes is intense euphoria.[35]

Manic symptoms may bolster creative productivity. Creativity was specifically related to more adaptive symptoms of mania, such as increased activity, excitement, less need for sleep, engagement in new activity, enhanced thinking, and faster thought processes. BD is related to many of these precursors to creativity, including elevated tendencies toward impulsivity, openness to experience, confidence, ambition, and positive mood states.[35] In the case of BD, however, it is likely that reducing severe manic episodes may actually enhance creativity in many individuals.[43] Research suggests relationships between creativity and affective illness, specifically BD.[44] BD is significantly overrepresented among samples of authors, poets, and visual artists. About 8.2% of those in creative professions (including architecture/design, musical composition, musical performance, theatre, fiction writing, expository writing, and poetry) appeared to have had experiences of mania.[45] Thus, “Geetaani bhajate nityam” of PU represents creativity or musical abilities found in the patients of mania.

Vinagna bhava (nudity/exhibitionism)

Vinagna bhava” of PU represents nudism or exhibitionism or disinhibition, which are commonly found in mania and dementia. Sexual or erotic excitement has been noted as a feature of mania. Hypersexuality is an accepted symptom of mania, but more subtle forms may be easily missed when screening patients. Hypersexuality is listed as part of the diagnostic criteria for BD.[46] Manic symptoms of BD may also present a risk of judicial complication because of patients' behavioral and sexual disinhibition, which may lead to hypersexuality, excessive familiarity, or exhibitionism.[30] Mania is characterized by reckless behavior such as impulsive spending and sexual indiscretions.[34]

Vinidra (insomnia/decreased need for sleep)

Vinidra” is mentioned as the feature of PU in “Sushruta samhita” only.[4] Decreased need for sleep is one of the seven diagnostic criteria of BD/mania. Although the ability to maintain energy without sleep is characteristic of mania, manic patients still likely require sleep to sustain life. Historical data suggest that manic patients, despite prolonged sleeplessness, ultimately have a physiological need for sleep. Disruption of the daily rhythm may often occur before episodes of mania in bipolar patients. Sleep disturbance, regardless of the underlying mechanism, is of important in the management of patients with BD.[47] Constant activity and a reduced need for sleep prevent proper rest. Although short periods of sleep are possible, some patients may not sleep for several days in a row.[14] The person during manic episode awakens several hours with felling full of energy. When the sleep disturbance is severe, the person may go for days without sleep and yet not feel tired.[48] Decreased need for sleep found in mania resembles with “Vinidra” of PU.

Pashyati taarakaa diva (seeing stars in the sky during daytime/visual hallucinations)

“Pashyate taarakaa diva” (perceiving stars during daytime in the sky) is mentioned in “Sushruta samhita [4] as one of the features of PU whereas “Asatyajwalana, jwala, taarakaa darshanam” (perceiving fire, lighting and stars in their absence) has been mentioned by “Vagbhata.”[5-6] These features indicate perceiving things which does not exist in reality, i.e., “visual hallucinations.” Psychotic mania is characterized by four items: abnormalities in thought content, appearance (impaired self-care), poor sleep, and speech abnormalities (rate and amount). Most of the psychotic phenomena are included in the item “thought content,” which describes grandiose and paranoid ideas, ideas of reference, delusions, and hallucinations. Psychotic mania is conceptualized as a more severe form of mania and it is associated with poorer levels of social functioning.[26] Delusions or hallucinations whose content is in consistent with the typical manic themes such as inflated worth, power, knowledge, and identity or special relationship to a popular person or deity are considered as mood-congruent psychotic features. Delusions and hallucinations whose content does not involve typical manic themes such as inflated worth, knowledge, power, and identity are called as mood-incongruent psychotic features.[48]

Visual hallucinations occur in a wide variety of neurological and psychiatric disorders, including toxic disturbances, drug withdrawal syndromes, focal central nervous system lesions, migraine headaches, schizophrenia, blindness, and psychotic mood disorders. Visual hallucinations range from simple and elemental, in which hallucinations consist of flashes of light or geometrical figures to elaborate visions such as a flock of angels. Manic depressive patients report mainly auditory and visual hallucinations believed to be less real in retrospect, less controllable, sometimes involving marked changes in time sense and with vague causes ascribed, but nearly always considered to be experienced only by them. Elaborate visual hallucinations in BD during the manic phase were also found.[49]Pashyate taarakaa diva” and “Asatya jwalana, jwala, taarakaa darshanam” of PU indicate psychotic mania or mood disorder with psychotic features.

Atyugram/Teevra vegam (acute onset/severe)

Atyugram” (very severe) and “Aashu kuryat” (acute in onset) are explained in the samprapti (pathogenesis) of PU in “Charaka samhita.” “Anaatmakasya” is also mentioned in samprapti of PU which means “a person who does not have self-control” or “person having a low self-esteem” or “vulnerable personality traits” or “weak mindedness.”[3] Acute onset and severity in nature are the characteristic features of PU.[3] Manic episodes typically begin suddenly, with a rapid escalation of symptoms over a few days. Frequently, manic episodes occur following psychosocial stressors, and in adolescents, they may be associated with psychotic features, school truancy, antisocial behavior, school failure, and substance abuse. It was found that significant proportion of adolescents appear to have a history of long-standing behavior problems that precede the onset of a frank manic episode (this indicates vulnerability to tolerate stress or “Anaatmakasya”). Manic episodes usually last from a few weeks to several months and are briefer and end more abruptly.[48]Atyugram, “ “Aashu kuryat, “ and “Anaatmakasya” mentioned in the samprapti of PU represent the acute onset, severity in nature, and vulnerable personality traits found in the patients of manic episode.

Other symptoms of PU such as Vahni shankee (suspects fire/delusions), Bahu bhuk (voracious or excessive eating), Santaapa/Aushnya/Daaha bahula/Trishna bahula/Udaka, pracchhaya sheetabhilasha/Jalaantara vihaara sevi (raised body temperature/feeling of burning sensation/excessive thirst/fond of shade and cold items), Sweda bahula (excessive sweating), Samrabdhakshata (overwhelmed/swelled/agitated/ furious eyes), and Taamra, harita, haridra, peeta varnata of eyes and skin (coppery, greenish, yellowish discoloration of eyes and skin) etc denotes an underlying organic pathology. The physiological signs and symptoms of PU represent hyperthyroidism and psychological signs and symptoms of PU represent manic episode [Table 3]. It seems that the condition of PU is not “manic episode” or BD alone, but it seems to be a “manic episode due to some general medical condition.” The clinical presentation of PU represents “hyperthyroidism with mania.”


  Comorbidity of Hyperthyroidism With Mania Top


Some patients with hyperthyroidism develop mania-like symptoms. Such patients can be diagnosed with “mood disorders due to hyperthyroidism” because the symptoms of depressive and BDs are the direct physiological effects of hyperthyroidism. Elevated thyroid hormone level has direct effect on mood. History of hyperthyroidism increases the risk of subsequent onset of idiopathic BD.[50] Thyroid diseases can trigger psychiatric illnesses such as anxiety, depression, mania, and psychosis. Manic symptoms have been known to occur with hyperthyroidism. In hyperthyroidism, late-onset mania is more commonly detected than early-onset mania. Manic symptoms may gradually develop in the wake of thyroid hormone excess.[51]

Multiple cases of patients with thyrotoxicosis presenting with symptoms clinically indistinguishable from bipolar mania have been reported. A patient with thyrotoxicosis with bipolar mania reported decreased sleep (vindira), hypersexuality (vinagna bhava), mood lability (krodha/rosha), increased spending, impulsive behavior (samrambha), and psychotic symptoms such as paranoid ideations and delusions (vahni shakee).[52] Subjects with thyroid disease and a positive family history of mood disorders have also been reported as suffering from mania and hypomania, depression, OCD, and organic mental disorders such as delirium.[53] A vast majority of patients with hyperthyroidism will display a psychiatric disorders such as anxiety, manias or depression.[54] Hyperthyroidism may contribute to the manic episode or precipitate a manic episode in a patient predisposed to BD.[55] There is an increased risk of affective disorders following the diagnosis of hyperthyroidism and vice versa.[56]


  Graves' Disease and Its Comorbidity With Mania Top


GD is a syndrome characterized by hyperthyroidism, a particular ophthalmopathy and pretibial myxedema. Usually, thyroid enlargement, goiter, and excessive thyroid hormone action are the features of the illness.[57] Many characteristic signs and symptoms of GD result from elevated thyroid hormone levels. Symptoms and signs result from hyperthyroidism are a consequence of underlying autoimmunity. Weight loss, fatigue, heat intolerance, tremors, and palpitations are the most common symptoms.[58] Graves' ophthalmopathy is an organ-specific autoimmune process strongly linked to Graves' hyperthyroidism.[59] Thyrotoxicosis commonly presents with anxiety, dysphoria, emotional lability, intellectual dysfunction, and mania. Mania may also be observed in hyperthyroidism. Severe hyperthyroidism can result in thyroid storm, a condition that ranges in neuropsychiatric presentation from hyperirritability, anxiety, and confusion. Patients with remitted hyperthyroidism had significantly shown more anxiety, hostility, mania, and sleep disturbances compared with controls. Subclinical hyperthyroidism may be associated with nervousness and irritability even mild thyroid dysfunction has been associated with changes in mood.[60] Serious psychiatric symptoms include manic excitement, delusions, and hallucinations. Many patients with affective disorders have noticeable abnormalities in the hypothalamic–pituitary–thyroid (HPT) axis.[51]

Inflammation, autoimmunity, Graves' disease, and etiology of Pittaja Unmada

The peripheral pathophysiology of BD appears to be related to systemic inflammatory mechanisms. Moreover, inflammation has been proposed to be a causative factor for BD progression. Persistent low-grade inflammation is more intense during mood episodes, especially during manic episodes. Hypothalamic–pituitary–thyroid axis abnormalities are common in BD. Bipolar patients experiencing mania had higher peripheral inflammatory indices. Diagnosis of bipolar I disorder during manic episodes have immune system activation, hemodilution, and abnormal thyroid functions.[61]

Hyperthyroidism is most often caused by autoimmunity, as in GD or by one or more autonomously functioning thyroid nodules. It has been suggested that the increased risk of psychiatric comorbidity observed in subjects with thyroid autoimmunity could be due to autoimmunity per se rather than due to the thyroid state.[56] Symptoms and signs result from hyperthyroidism are a consequence of underlying autoimmunity.[58] GD typically includes two major categories of phenomena. Those specific to GD and caused by the autoimmunity per se include the exophthalmos, thyroid enlargement and thyroid stimulation, and the dermal changes. The second set of problems is caused by the excess thyroid hormone. This thyrotoxicosis or hyperthyroidism does not differ from that induced by any other cause of excess thyroid hormone.[57]

By considering the above facts, it is evident that inflammation and autoimmunity plays a significant role in the manifestation of thyroid disease, especially GD. Various systemic inflammatory mechanisms were also found in BD or manic episode. Excessive indulgence of ajeerna, amla, katu, ushna, and vidahi type of foods explained in the nidana of PU leads to pitta prakopa (aggravation of pitta dosha)[3] and provokes systemic inflammatory response or autoimmune reactions in the body which further leads to thyroid disease (especially GD) and/or BD. Hypothetically, it can be assumed that nidana of PU leads to autoimmune thyroiditis or GD and also provokes systemic inflammatory responses.

Physiological signs and symptoms of Pittaja unmada

Vahni shankee (suspects fire/delusions)

Vahni shankee” means feeling of burning sensation or feeling of extreme burning like self-ablaze or suspecting fire even when seated in cold water or seeing fire in the absence of it.[4],[5],[6] This symptom has two contextual meanings, either feeling of extreme burning sensation (physiological such as neuropathy) or suspecting fire (delusion/paranoid ideation) or visualizing fire in the absence of it (visual hallucination). Paranoid ideations and delusions along with the features of hyperthyroidism such as heat intolerance and elevated body temperature are found in a patient suffering from thyrotoxicosis associated with bipolar mania.[52] Severe hyperthyroidism can lead to acute polyneuropathy. Nerve conduction studies revealed mixed axonal and demyelinating polyneuropathy in both the motor and sensory nerves. The pathogenesis of neuropathy in hyperthyroidism is still obscure. It has been postulated to be either a direct effect of excessive thyroid hormones, immune mediated, or due to a hypermetabolic state depleting the nerves of essential nutrients.[62] It is evident that “Vahni shankee” in hyperthyroidism patients represents neuropathy, and in patients of BD or mania, it represents paranoid delusions or visual hallucinations.

Bahu bhuk (voracious or excessive eating)

Bahu bhuk” is explained as one of the features of PU by “Sushruta” only.[4] It represents excessive appetite or excessive eating. Increased appetite is found in thyrotoxicosis patients.[51] Elevated mood, decreased sleep, increased energy levels, and excessive psychomotor activities during manic episode demand more calories to achieve that patient may indulge in excessive eating. Hyperthyroidism increases energy expenditure and reduces body weight. Traditionally, it has been assumed that it is this reduced body weight that drives the hyperphagia that can be a presenting feature in hyperthyroidism.[63] Thus, hyperphagia or “Bahu bhuk” is seen in hyperthyroidism and also can be seen in mania.

Santaapa/Aushnya/Daaha bahula/Sweda bahula/Trishna bahula/Udaka, pracchhaya sheetabhilasha/Jalaantara vihaara sevi (raised body temperature/feeling of burning sensation/excessive perspiration/excessive thirst/fond of shade and cold items)

Elevated body temperature, increased perspiration, and heat intolerance are found in thyrotoxicosis patients[51] and they represent “santaapa/aushnya,”sweda bahula,” and “jalaantara vihaara sevi/udaka, pracchhaya sheetabhilasha” of PU. There is an imbalance of fluid and electrolyte homeostasis among bipolar episodes, which is suggestive of relative hemodilution during manic episodes.[64] Disturbances of fluid and electrolyte balance have been reported in acute exacerbations of BD. Alterations in water and electrolyte homeostasis during acute mood episodes have been attributed to redistribution of electrolyte and water within body compartments, changes in fluid and solute intake, and altered fluid and electrolyte metabolism. Arginine vasopressin (AVP) has been considered to have a key role in the pathogenesis of mood disorders. Regulation of serum osmolarity is particularly maintained by the antidiuretic effect of the hormone AVP. During increased osmolarity, AVP is released by the pituitary gland, and an inappropriate increase of AVP causes hyponatremia and hemodilution. It has been found that AVP function is augmented in manic and diminished in depressive episodes. During manic episodes, the hemoglobin, hematocrit, albumin, and sodium concentrations were lower than in depressive episodes, suggesting that the manic state is characterized by a relative hemodilution. Manic episodes have been associated with decreased levels of hematological and biochemical parameters, which might reflect a relative hemodilution.[65]

Even though the neurobiological mechanisms underlying the etiology of BD are not understood completely, the dopamine hypothesis has been the leading key theory for manic episode. The antimanic actions of antidopaminergic drugs provide crucial evidence for a hyperdopaminergic state in mania. Another important function of dopamine outside the central nervous system is regulation of renal electrolyte homeostasis. The renal dopaminergic system plays a key role in water and sodium balance by interacting renal renin–angiotensin system and vasopressin. Dopamine is also a linking point in the association between mood states and water–electrolyte homeostasis. Mania is associated with diminished levels of serum/plasma parameters, such as hemoglobin, hematocrit, albumin, sodium, and total protein. There is a significant decrement for serum osmolarity in patients with an acute manic episode, compared with healthy control subjects. Mania is associated with pathological variations in body weight, retention of water, and is accompanied by pathological thirst (trishna bahula).[65] Santaapa/aushnya, sweda bahula, trishna bahula, udaka pracchhaya sheetabhilasha, jalaantara vihara sevi etc., features of PU have shown similarity with the features of hyperthyroidism or mania such as elevated body temperature, excessive perspiration, excessive thirst or dehydration or fluid and electrolyte imbalance and heat intolerance etc.

Samrabdhakshata (overwhelmed/swelled/agitated/furious eyes)

Samrabdhakshata” denotes anxious/worried or agitated or hyperalert or tired (due to sleeplessness) eyes seen in manic patients. Graves' ophthalmopathy is an organ-specific autoimmune process strongly linked to Graves' hyperthyroidism. Eyelid retraction, proptosis, periorbital edema, chemosis, and disturbances of ocular motility are seen in Graves' ophthalmopathy.[59] Thus, “Samrabdhakshata” may represent the agitated or tired eyes seen in mania or it may be Graves' ophthalmopathy.

Taamra, harita, haridra, peeta varnata of eyes and skin (coppery, greenish, yellowish discoloration of eyes and skin)

Taamra (coppery), harita (green), haridra (turmeric yellow), and peeta (yellow) discoloration of eyes and skin are one of the characteristic features of PU. Thyrotoxicosis is associated with cutaneous manifestations. Although certain manifestations are specific to GD, thyrotoxicosis of any etiology can include skin sequelae. Hyperpigmentation has been described in thyrotoxicosis patients in both localized and generalized distribution similar to that of Addison disease. There is a speculation that the hyperpigmentation is due to increased release of pituitary adrenocorticotropic hormone compensating for accelerated cortisol degradation. Patients with GD may have distinctive cutaneous findings related to autoimmune attack on skin and other tissues. Thyroid dermopathy (TD) usually reflects severe GD. The most common locations for TD are the pretibial area, distal lower extremities, upper extremities, shoulders, back, ears, nose, and scar tissues. The lesions in TD are raised and waxy with coloring ranging from light to yellowish brown. The discoloration of eyes and skin mentioned in PU is similar to hyperpigmentation seen in thyrotoxicosis.[66]


  Management of Pittaja Unmada Top


Ayurveda has described “Daiva vyapashraya chikitsa” (spiritual/divine therapy), “Sattvavajaya chikitsa” (Ayurvedic psychotherapy), and “Yukti vyapashraya chikitsa” (rational use of drugs, diet, and activities) for the management of Unmada (psychiatric disorders). Yukti vyapashraya chikitsa includes samshodhana (body cleansing procedures like panchakarma) and samshamana (pacifying doshas by internal medicines, diet, and/or activities). Patients suffering with unmada should be treated with snehana (oleation), swedana (sudation) and then subjected for evacuation with drastic emetics or purgatives. For the management of PU, “Virechana karma” (therapeutic purgation) is advised after undergoing snehana and swedana. Samsarjana karma (standard dietary protocol) should be given after virechana. Virechana karma plays a pivotal role in the management of PU and it stabilizes mood by reducing manic episode-related symptoms such as anger, restlessness, and hostility. According to a previous case report, virechana improves the quality of life of BPAD patients, especially in domains such as energy levels, concentration, memory, sleep, and other physical and psychological parameters. “Mamsyadi kwatha,” “Maha kalyanaka ghrita,” “Sarpagandha” (Rauwolfia serpentina), “Shankhapushpi” (Convolvulus pluricaulis), and “Guduchi” (Tinospora cordifolia) were also found to be effective in the management of PU or BPAD.[23]


  Conclusion Top


PU is described in all Ayurvedic classical texts. The etiopathology of PU seems to induce systemic inflammatory sequelae and also autoimmune reactions which again lead to the manifestation of autoimmune thyroid disease or GD. Signs and symptoms of PU can be classified into two groups, psychological and physiological. The psychological and physiological features of PU have shown similarity with conditions like manic episode, bipolar disorder (BD), GD, thyrotoxicosis and hyperthyroidism. PU is similar to “psychotic mania” or “mood disorder with psychotic features” or “manic episode due to general medical condition” or “BD comorbid with hyperthyroidism or GD.” PU can be managed successfully with “Virechana” followed by internal medicines.

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Conflicts of interest

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