Yoga as an adjunct treatment for BPAD

Patients suffering from psychological issues are constantly on the lookout for newer treatment options. The most common reasons are as follows

1. Slow onset of action and low to moderate efficacy of the currently available medication.
2. Poorly explained and understood details of how the medication actually works.
3. Uncertainty on how long to use the medication once initiated.
4. Effort and time that needs to be put into therapies
5. Fear of side effects.

One such alternative treatment that is being tried by a lot of patients with bipolar disorder (BD) is Yoga. People have tried it as a standalone treatment or as an adjunct to medication/therapy. Scientific literature currently available does not give us a definitive answer to whether it is helpful or harmful as people have reported both feeling better and worse after trying this form of treatment. 

As with most therapies and techniques which aim to improve mental health, yoga could be beneficial if it is done with proper guidance and in conjunction with therapy or/and medication. 

References:

• Jean M, Umair M, Muddaloor P, Farinango M, Ansary A, Dakka A, Nazir Z, Shamim H, Paidi G, Khan S. The Effects of Yoga on Bipolar Disorder: A Systematic Review. Cureus. 2022 Aug 4;14(8):e27688. doi: 10.7759/cureus.27688. PMID: 36072189; PMCID: PMC9440796.
• Uebelacker LA, Weinstock LM, Kraines MA. Self-reported benefits and risks of yoga in individuals with bipolar disorder. J Psychiatr Pract. 2014 Sep;20(5):345-52. doi: 10.1097/01.pra.0000454779.59859.f8. PMID: 25226195.

Iloperidone for Bipolar Disorder

Most recent medication to be approved for bipolar disorder is an atypical anti-psychotic, Iloperidone. To be more specific, this drug was approved by the US Food and Drug Administration for treatment of manic or mixed episodes associated with bipolar I disorder in adults. This can be considered a significant development because new medications and treatments in the field of psychiatry are few.

Iloperidone is an atypical anti-psychotic, with a mixed D2/5HT2A antagonism as its mechanism of action. It was first approved for acute treatment of schizophrenia in adults. 

References:

•  Vanda Pharmaceuticals' Fanapt (iloperidone) receives US FDA approval for the acute treatment of bipolar I disorder. News release. Vanda Pharmaceuticals Inc. April 2, 2024. Accessed April 2, 2024. https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-fanapt-iloperidone-receives-us-fda-approval-for-the-acute-treatment-of-bipolar-i-disorder-302106405.html
• Torres R, Czeisler EL, Chadwick SR, Stahl SM, Smieszek SP, Xiao C, Polymeropoulos CM, Birznieks G, Polymeropoulos MH. Efficacy and Safety of Iloperidone in Bipolar Mania: A Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. 2024 Jan 15;85(1):23m14966. doi: 10.4088/JCP.23m14966. PMID: 38236020.

Solar radiation and Bipolar Disorder

There has been much interest recently in investigating the role of environmental variables (ex. sunlight exposure, photo-period and solar radiation) in bipolar disorder (BD) patients. Studies have found a significant impact on both the onset and course of BD and also on sleep-wake cycle, mood and energy levels.

It is well recognized that a lot of BD patients tend to show a seasonal vulnerability, as described in Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM 5) within the specifier criteria of BD. 

One possible mechanism that could explain this phenomenon is the exposure to UV-B and better vitamin D levels, which may have a protective role in the development of bipolar disorder. 

There is also evidence that shows increased exposure to solar radiation and the resultant weather conditions results in an earlier age of onset of BD.

There is a need for further, more conclusive studies in this subject.

References:

• Aguglia A., Borsotti A., Maina G. Bipolar disorders: Is there an influence of seasonality or photoperiod? Rev. Bras. Psiquiatr. 2018;40:6–11. doi: 10.1590/1516-4446-2016-2144
• Bauer M., Glenn T., Alda M., Andreassen O.A., Angelopoulos E., Ardau R., Baethge C., Bauer R., Baune B.T., Bellivieri F., et al. Influence of light exposure during early life on the age of onset of bipolar disorder. J. Psychiatr. Res. 2015;64:1–8. doi: 10.1016/j.jpsychires.2015.03.013.
• Geoffroy P.A., Bellivier F., Scott J., Etain B. Seasonality and bipolar disorder: A systematic review, from admission rates to seasonality of symptoms. J. Affect. Disord. 2014;168:210–223. doi: 10.1016/j.jad.2014.07.002.
• Bauer M, Glenn T, Achtyes ED, Alda M, Agaoglu E, Altınbaş K, Andreassen OA, Angelopoulos E, Ardau R, Aydin M, Ayhan Y, Baethge C, Bauer R, Baune BT, Balaban C, Becerra-Palars C, Behere AP, Behere PB, Belete H, Belete T, Belizario GO, Bellivier F, Belmaker RH, Benedetti F, Berk M, Bersudsky Y, Bicakci Ş, Birabwa-Oketcho H, Bjella TD, Brady C, Cabrera J, Cappucciati M, Castro AMP, Chen WL, Cheung EYW, Chiesa S, Crowe M, Cuomo A, Dallaspezia S, Del Zompo M, Desai P, Dodd S, Etain B, Fagiolini A, Fellendorf FT, Ferensztajn-Rochowiak E, Fiedorowicz JG, Fountoulakis KN, Frye MA, Geoffroy PA, Gitlin MJ, Gonzalez-Pinto A, Gottlieb JF, Grof P, Haarman BCM, Harima H, Hasse-Sousa M, Henry C, Hoffding L, Houenou J, Imbesi M, Isometsä ET, Ivkovic M, Janno S, Johnsen S, Kapczinski F, Karakatsoulis GN, Kardell M, Kessing LV, Kim SJ, König B, Kot TL, Koval M, Kunz M, Lafer B, Landén M, Larsen ER, Lenger M, Licht RW, Lopez-Jaramillo C, MacKenzie A, Madsen HØ, Madsen SAKA, Mahadevan J, Mahardika A, Manchia M, Marsh W, Martinez-Cengotitabengoa M, Martini J, Martiny K, Mashima Y, McLoughlin DM, Meesters Y, Melle I, Meza-Urzúa F, Mikolas P, Mok YM, Monteith S, Moorthy M, Morken G, Mosca E, Mozzhegorov AA, Munoz R, Mythri SV, Nacef F, Nadella RK, Nakanotani T, Nielsen RE, O'Donovan C, Omrani A, Osher Y, Ouali U, Pantovic-Stefanovic M, Pariwatcharakul P, Petite J, Petzold J, Pfennig A, Ruiz YP, Pinna M, Pompili M, Porter RJ, Quiroz D, Rabelo-da-Ponte FD, Ramesar R, Rasgon N, Ratta-Apha W, Ratzenhofer M, Redahan M, Reddy MS, Reif A, Reininghaus EZ, Richards JG, Ritter P, Rybakowski JK, Sathyaputri L, Scippa AM, Simhandl C, Smith D, Smith J, Stackhouse PW Jr, Stein DJ, Stilwell K, Strejilevich S, Su KP, Subramaniam M, Sulaiman AH, Suominen K, Tanra AJ, Tatebayashi Y, Teh WL, Tondo L, Torrent C, Tuinstra D, Uchida T, Vaaler AE, Vieta E, Viswanath B, Yoldi-Negrete M, Yalcinkaya OK, Young AH, Zgueb Y, Whybrow PC. Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder. Int J Bipolar Disord. 2023 Jun 22;11(1):22. doi: 10.1186/s40345-023-00303-w. PMID: 37347392; PMCID: PMC10287592.

Neurological soft signs in bipolar disorder

Q: What are neurological soft signs (NSS)?
Ans. These include subtle deficits of motor coordination, sensory integration and sequencing of complex motor acts. 

Q. Why are these called "soft" signs?
Ans. These are termed soft signs because they cannot be localized to a particular area in the brain.

Q. Why are these being studied?
Ans. NSS are being studied in a variety of psychiatric illnesses because they might have a bearing on severity of symptoms and clinical outcome of psychiatric illnesses such as bipolar disorder

References

• Chrobak AA, Soltys Z, Dudek D, Siwek M. Neurological and cerebellar soft signs in bipolar disorder: The role of staging, type and history of psychotic symptoms. Prog Neuropsychopharmacol Biol Psychiatry. 2023 Mar 8;121:110673.
• Negash, A., Kebede, D., Alem, A., Melaku, Z., Deyessa, N., Shibire, T., Fekadu, A., Fekadu, D., Jacobsson, L. and Kullgren, G., 2004. Neurological soft signs in bipolar I disorder patients. Journal of affective disorders, 80(2-3), pp.221-230.

Bipolar Disorder - Signs and symptoms of the initial prodrome

Following are the common signs and symptoms of Bipolar Disorder (prodrome)

• Irritability and aggressiveness
• sleep disturbances
• depression and mania symptoms/signs
• hyperactivity
• anxiety
• mood swings 

Ref: Skjelstad DV, Malt UF, Holte A. Symptoms and signs of the initial prodrome of bipolar disorder: a systematic review. J Affect Disord. 2010 Oct;126(1-2):1-13. doi: 10.1016/j.jad.2009.10.003. Epub 2009 Nov 1. PMID: 19883943.

Bipolar Disorder - Differential Diagnoses

 Following organic and functional disorders might mimic symptoms of Bipolar Disorder

• Anxiety disorders (ex. generalized anxiety disorder, panic disorder etc.)
• Hyperthyroidism
• Cushing's disease/ syndrome
• Multiple sclerosis
• Post Traumatic Stress Disorder
• Schizo-affective disorder
• Schizophrenia
• Attention Deficit Hyperactivity Disorder

Ref: 

1. World Health Organization(WHO). (1993). The ICD-10 classification of mental and behavioural disorders. World Health Organization.
2. Price AL, Marzani-Nissen GR. Bipolar disorders: a review. Am Fam Physician. 2012 Mar 1. 85(5):483-93

Bipolar Disorder - Types (DSM-5)

 Bipolar Disorder, as per the Diagnostic and statistical manual of mental disorders (5th ed.), includes the following types

1. Bipolar 1 : this is diagnosed when symptoms of mania last 7 days or more. Also, can be diagnosed when an individual has severe mania which requires hospitalization. 
2. Bipolar 2 : diagnosed when an individual has symptoms of hypomania, preceded or followed by a major depressive episode
3. Cyclothymic disorder : Includes symptoms of hypomania and depression that last for 2 years or more in adults, not severe enough to warrant a diagnosis of the above 2 conditions. 

Ref:

1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596

Bipolar Disorder - Introduction

 It is a psychological disorder, coded as F31 in ICD 10 [1], characterized by unusual and pervasive changes in their mood. A person suffering from biploar disorder can go from feeling extremely sad to feeling extremely happy within a few days or in some case, in a few hours. 

Symptoms of this disorder are spread over a spectrum. Someone with severe symptoms, is easy to diagnose while diagnosing someone who is on the lower side of this spectrum is challenging. 

Ref:

1. World Health Organization(WHO). (1993). The ICD-10 classification of mental and behavioural disorders. World Health Organization.

Treatment of Malaria In India - Update part 2

Treatment of Severe Plasmodium Falciparum Malaria 

Should not be treated on out patient basis, as it requires parenteral administration of antimalarials and has a risk of mortality. 

1. Artesunate: It is the drug of choice. It should be given in a dose of 2.4 mg/kg IV on admission (0 hour), then at 12 hours and 24 hours and then once daily till the patient takes orally or for 7 days. Then, they should get full course of ACT for 3 days (Table 1). However, ACT containing MQ should be avoided in cerebral malaria due to possibility of development of neuropsychiatric complication

2. Quinine: It is an acceptable alternative to AS. It should be given at a dose of 20 mg quinine salt/kg of body weight in 5% dextrose/dextrose saline, over 4 hours, on admission. It is followed by 10 mg/kg of body weight 8 hourly infusions which should be started 8 hours after the 1st loading dose. The infusion rate should not exceed 5 mg/kg of body weight/hour. Initial loading dose should not be given if patient has already taken quinine. If quinine therapy is used beyond 48 hours, the dose should be reduced to 7 mg/kg of body weight 8 hourly till patient takes orally. Then, he should be given oral quinine in a dose of 10 mg/kg of body weight 8 hourly to complete 7 days of therapy. Quinine injection must not be given as bolus injection. It is always given in IV infusion. Doxycycline in a dose of 3 mg/kg of body weight per day for 7 days is to be added when the patient starts taking orally. Doxycycline is contraindicated in pregnancy and children below 8 years of age. In those cases, instead of doxycycline, clindamycin is to be given in a dose of 10 mg/kg of body weight 12 hourly for 7 days

3. Artemether: It should be given in the dose of 3.2 mg/kg of body weight intramuscularly on admission and 1.6 mg/kg of body weight intramuscularly once per day for 4 more days. Then, ACT is to be given for 3 days

4. Alpha-beta artemether: It should be given in a dose of 150 mg/day for 3 days intramuscularly. It is not recommended for children. It should be followed by ACT for 3 days. 

References

1. Guidelines for the Treatment of Malaria 2010 (2nd edition). World Health Organization, 20, Avenue Appia-CH-1211 Geneva 27.

2. Guidelines for Diagnosis and Treatment of Malaria in India 2011 (2nd edition). Government of India, National Institute of Malaria Research, New Delhi.

Treatment of Malaria In India - Update part 1

I had posted treatment guidelines for malaria in 2014, as per the existing guidelines. 

Newer guidelines have been introduced since. Hence, this update. 

1. Treatment of Uncomplicated Plasmodium Falciparum Malaria 

Artemisinin combination therapy (ACT) is the drug of choice for all confirmed cases of uncomplicated PF cases. This should be combined with primaquine (PQ) (0.75 mg/kg body weight or 45 mg) on day-2. The ACT recommended in the National Program in India is artesunate (AS) + sulfadoxine and pyrimethamine (SP). Oral AS monotherapy is banned in India.

2. Treatment of Uncomplicated Plasmodium Vivax malaria

Chloroquine is the drug of choice of Plasmodium vivax (PV) cases. It is given at a dose of 10 mg/kg (600 mg) on day-1 and day-2 and 300 mg on day-3. Primaquine at a dose of 0.25 mg/kg (15 mg/day) for 14 days is tobe added to prevent relapse. Primaquine is contraindicated in G6PD deficiency cases, infants and pregnant women.

Post CoViD complex

Post CoViD complex is a cluster of conditions which may effect a person convalescing from active CoViD infection, 4 or more weeks after the initial infection. The initial may or may not be clinically detectable. As this is an evolving disease and not much definitive research has been done, we are still finding newer and varied conditions, causation of which  is not otherwise explainable. 

According to the information on the CDC USA website, there can be 2 types of symptoms

1. New symptoms

2. Ongoing symptoms

New Symptoms - These are the symptoms which were not present during the initial infection period and have arisen 4 weeks after that. 

Ongoing Symptoms - These are the symptoms which started during the initial infection and never completely went away after the initial infection. 

Following is a list of common symptoms 

1. Difficulty breathing or shortness of breath
2. Tiredness or fatigue
3. Symptoms that get worse after physical or mental activities (also known as post-exertional malaise)
4. Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
5. Cough
6. Chest or stomach pain
7. Headache
8. Fast-beating or pounding heart (also known as heart palpitations)
9. Joint or muscle pain
10. Pins-and-needles feeling
11. Diarrhea
12. Sleep problems
13. Fever
14. Dizziness on standing (lightheadedness)
15. Rash
16. Mood changes
17. Change in smell or taste
18. Changes in menstrual period cycles

Prevention

The best way to prevent post-CoViD conditions is to prevent COVID-19 illness.

Source - National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases

Radiation Terrorism Part 2

Types of Contamination

It can be of 3 types

• Whole body exposure
• External
• Internal

1. Whole body exposure
• Gamma rays, x-rays and neutrons which can penetrate through the body and cause severe tissue damage.
2. External contamination
• Effects body surface, clothing, skin, and hair.
• This is the main thing to be concerned about in a radioactive terrorist strike.
• These consist mainly of alpha and beta radiation.
• Alpha particles cause surface burns only.
• Beta particles can cause cutaneous burns and scarring.

More on Internal contamination in my next post. 

Radiation Terrorism Part 1

Types of Radio-isotopic Radiation

4 main types viz.

• alpha
• beta
• gamma
• neutrons.

1. Alpha radiation - 
• These are positively charged particles, with 2 protons and 2 neutrons.  
• Large particles, so they have limited penetrating power.
• If internalized, they can cause significant cellular damage.
2. Beta radiation - 
• Negatively charged particles consisting of electrons.
• Penetrating power depends on their energy.
• A good example is radioactive iodine released in nuclear plant accidents.
• They can cause a burn (similar to a thermal burn and is treated as such)
3. Gamma rays and x-rays (both photons) - 
• Gamma rays are uncharged electromagnetic radiation discharged from a nucleus as a wave or photons of energy.
• X-rays are the product of abrupt mechanical deceleration of electrons striking a heavy target such as tungsten.
• Both travel easily through matter, high penetrating power.
4. Neutron particles - 
• These are heavy and uncharged, often emitted during nuclear detonation.
• Ability to penetrate tissues is variable, depending on their energy.

Treatment of Malaria in India

1. Uncomplicated Malaria (sensitive to chloroquine)
P. vivax – chloroquine 25 mg/kg over 3 days + Primaquine 0.25 mg/kg OD for 14 days
P. falciparum - chloroquine 25 mg/kg over 3 days + Primaquine 45 mg single dose

2. Uncomplicated Malaria (chloroquine resistant)
Artemisinin Combination Therapy (ACT) i.e Artesunate 50 mg + Sulfadoxine 500 mg + Pyrimethamine 25 mg for 3 days

3. Severe Malaria
Artesunate- 2.4 mg/kg @ 0 hrs, 1.2 mg/kg @ 12 hrs, 24 hrs, then OD, IV/IM
Quinine- LD:20 mg/kg, MD:10 mg/kg, both in 5% Dextrose
Artemether- 3.2 mg/kg IM on day 1, then 1.6 mg/kg IM OD
ab Arteether- 150 mg daily i.m. for 3 days in adults only
Switch to oral anti-malarials as soon as condition improves

Hypersplenism

Condition in which spleen removes circulating RBCs, granulocytes and platelets in excess quantity.

Diagnosis:

1. Pancytopenia
2. Normal or hypercellular bone marrow
3. Splenomegaly
4. Correction of cytopenias after splenectomy

Classification

1. Primary – when no aetiology for enlarged spleen is found.
2. Secondary –
1. Portal hypertension
2. Infiltrative disease, lymphoma, myelofibrosis
3. Hemolyitc anaemias, hematological disorders
4. Rheumatoid arthritis (Felty’s syndrome)
5. Tropical splenomegaly syndrome

Pathogenesis

When splenic size increases, there is increases pooling of blood in an environment with relatively reduced availability of nutrients but full of phagocytes.

This leads to exaggerated sequestration and destruction of cells leading to

1. Pancytopenia
2. Hemolysis
3. Increased plasma volume

Treatment

Therapy needed when cytopenias become severe and symptomatic

Treatment of underlying causes

Splenectomy if underlying cause cannot be corrected or treated

Type 1 Hypersensitivity

Type 1 Hypersensitivity

1. Eczema
2. Hay Fever
3. Asthma ( atopy )
4. Theobald Smith phenomenon
5. Anaphylactic shock
6. Acute dermatitis
7. Urticaria
8. Prusnitz kustner reaction
   

Behcet's Syndrome

It is a type of vasculitis

Symptoms:

1. Oral and genital ulcers 
   
2. Uveitis 
3. Optic atrophy

Pickwickian Syndrome:

It is a symptom complex presenting with the following symptoms:

1.Obesity 

2.Hypoventilation 

3.Somnolence 

4.Erythrocytosis

This comdition has been associated with sleep apnoea syndrome which has now been established as a separate entity.

Thoracic Aortic Aneurysm

Description:

Aabnormal dilatation of blood vessel

Pathogenesis:

Intimal tears progress to longitudinal intraluminal tears forming a lumen in the media.

There is collection of basophilic mucoid material in media and elastic tissue.

Most important factors promoting continued propagation of dissection are hypertension and velocity of left ventricular ejection.

Complications:

• Aortic rupture causing cardiac tamponade
  
• Leakage may cause pericarditis
  
• Dysphagia
  

Clinical Features:

• hypertension on initial presentation
  
• pericardial friction rub or AR murmur
  
• aortic insufficiency
  
• pulse deficit
  
• focal neurologic deficits may be present
  

Treatment:

1.Medical management for uncomplicated distal dissection

• sodium nitroprusside
• beta blockers
  

2.Surgery for acute proximal aortic dissection

• Operative repair to prevent rupture
  
• Emergency surgical repair for dissection of ascending aorta
  
• Cerebrospinal fluid drainage during and after surgery may reduce risk of neurological injury .
  

Idiopathic Intracranial Hypertension (IIH)

Description
Also called pseudotumor cerebri, benign intracranial and serous meningitis, it is a condition in which there is raised intracranial pressure in absence of space-occupying lesion, often presenting as headache and can potentially cause permanent visual loss.

Symptoms
Constant generalized severe headache
Transient visual obscurations (shadows, dark patches, or black spots in one or both eyes.
Pulsatile tinnitus
Visual sparkles (photopsia)
Diplopia

Signs
Papilledema
Enlarged blind spot.
Usually does not affect visual acuity.

Treatment
Most important aim of treatment is halting or preventing visual loss.
Weight reduction if obese.
Serial lumbar punctures can relieve syndrome.