Chronic pain and depression are both common conditions, and in many patients, they co-exist. This presentation looks at the link between chronic pain and depression. Various drugs that can be used to treat chronic pain/depression have been discussed, with a special emphasis on tricyclic antidepressants.
plain for treatment of patient with chronic pain, psychiatry and psychology are two approaches very important to have a proper treatment for pain disorders
New directions in the psychology of chronic pain managementepicyclops
Lecture followed audience discussion on contextual cognitive behaviour therapy and acceptance and commitment therapy in the management of chronic pain from the West of Scotland Pain Group on Wednesday 5th December 2007. The speaker is Lance M. McCracken PhD, of the Pain Management Unit at the Royal National Hospital for Rheumatic Diseases & University of Bath, Bath UK.
www.wspg.org.uk
Further reading:
DAHL, J., & LUNDGREN, T. (2006). Living beyond your pain using acceptance and commitment therapy to ease chronic pain. Oakland, CA, New Harbinger Publications.
http://www.worldcat.org/oclc/63472470
HAYES, S. C., STROSAHL, K., & WILSON, K. G. (1999). Acceptance and commitment therapy an experiential approach to behavior change. New York, Guilford Press.
http://www.worldcat.org/oclc/41712470
MCCRACKEN, L. M. (2005). Contextual cognitive-behavioral therapy for chronic pain. Progress in pain research and management, v. 33. Seattle, IASP Press.
http://www.worldcat.org/oclc/57564664
plain for treatment of patient with chronic pain, psychiatry and psychology are two approaches very important to have a proper treatment for pain disorders
New directions in the psychology of chronic pain managementepicyclops
Lecture followed audience discussion on contextual cognitive behaviour therapy and acceptance and commitment therapy in the management of chronic pain from the West of Scotland Pain Group on Wednesday 5th December 2007. The speaker is Lance M. McCracken PhD, of the Pain Management Unit at the Royal National Hospital for Rheumatic Diseases & University of Bath, Bath UK.
www.wspg.org.uk
Further reading:
DAHL, J., & LUNDGREN, T. (2006). Living beyond your pain using acceptance and commitment therapy to ease chronic pain. Oakland, CA, New Harbinger Publications.
http://www.worldcat.org/oclc/63472470
HAYES, S. C., STROSAHL, K., & WILSON, K. G. (1999). Acceptance and commitment therapy an experiential approach to behavior change. New York, Guilford Press.
http://www.worldcat.org/oclc/41712470
MCCRACKEN, L. M. (2005). Contextual cognitive-behavioral therapy for chronic pain. Progress in pain research and management, v. 33. Seattle, IASP Press.
http://www.worldcat.org/oclc/57564664
Via Christi Women's Connection presentation on advance in depression treatment by Matthew Macaluso, DO, medical director of Via Christi Psychiatric Clinic.
this presentation discusses pain pathways, definition and glossary of pain symptoms, classification of pain, pathogenesis, causes, diagnosis , types and treatment of neuropathic pain
illustrated with figures
TREATMENT RESISTANT DEPRESSION IS A AREA THAT IS NOT EXPLORED MUCH, BUT IT REALLY NEEDS LOT OF ATTENTION AS IT IS ONE OF THE MOST COMMON OBSTACLE IN ACHIEVING COMPLETE REMISSION IN DEPRESSION
Psychopharmacology and Cardiovascular Disease - psycho cardiologymagdy elmasry
Psychopharmacology andCardiovascular Disease.Your Heart And Mind Are Connected.Psychiatric Disorders and Cardiovascular System .Cardiac response to acute stress .Heart disease and depression are closely linkedCardiovascular Side Effects of Psychotropic Drugs
.
Via Christi Women's Connection presentation on advance in depression treatment by Matthew Macaluso, DO, medical director of Via Christi Psychiatric Clinic.
this presentation discusses pain pathways, definition and glossary of pain symptoms, classification of pain, pathogenesis, causes, diagnosis , types and treatment of neuropathic pain
illustrated with figures
TREATMENT RESISTANT DEPRESSION IS A AREA THAT IS NOT EXPLORED MUCH, BUT IT REALLY NEEDS LOT OF ATTENTION AS IT IS ONE OF THE MOST COMMON OBSTACLE IN ACHIEVING COMPLETE REMISSION IN DEPRESSION
Psychopharmacology and Cardiovascular Disease - psycho cardiologymagdy elmasry
Psychopharmacology andCardiovascular Disease.Your Heart And Mind Are Connected.Psychiatric Disorders and Cardiovascular System .Cardiac response to acute stress .Heart disease and depression are closely linkedCardiovascular Side Effects of Psychotropic Drugs
.
a detailed description of pain and therpaeutic options available and clinical assessment of pain, approach to the patient with pain, assessment of intensity of pain, nsaids and opioids, tca. WHO pain ladder, chronic opioid therapy
Pharmacology of Chronic Pain Treatment Addiction and Risks Michael Changaris
Currently, we are in the middle of an epidemic. More people die from addiction to pain medications then die from car accidents.
This lecture explores the biopsychosocial model of chronic pain. It includes pharmacotherapy, psychotherapeutic and other treatment modalities.
No poison can kill a positive thinker and no medicine can cure a negative thinker. Pain is a complex perceptual experience. Pain is a major public health problem. Beat back pain without surgery and conquer pain without painkillers. Delays have dangerous ends. Knee braces invite injury. Chronic pain affects one in three people in the United States. There are more Americans suffering from chronic pain than with diabetes, heart disease, and cancer combined. Chronic pain is caused by degeneration, illnesses, injuries, surgeries, and treatment side effects. Pain is a major public health problem and is the most common reason why Americans use complementary and integrative health practices. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. A migraine is associated with a modest increase in the risk of ischemic stroke.
Can read freely here
https://sethiortho.blogspot.com/
Complex Regional pain syndrome
Silas Mitchell
Causalgia.
Burning pain after a tramatic nerve injury combined with vaso motor, sudomotor and trophic changes
, Paul Sudeck identified the localized bone atrophy by x-rays (sudeck’s atrophy)
Because the inflammatory irritation which involves nutritional problems and in consequence resorption of bone
In 1917 a French surgeon named Rene Leriche implicated the sympathetic nervous system in Causalgia
He treated these patients with surgical sympathectomy
In the 1950’s, John Bonica introduced the phrase reflex sympathetic dystrophy
Complex: Varied and dynamic clinical presentation
Regional: Non-dermatomal distribution of symptoms
Pain: Out of proportion to the initiating events
Syndrome: Collection of symptoms and signs
CRPS – I Common presentation than CRPS -II
Reflex sympathetic dystrophy
CRPS – II Causalgia
Develops after injury to a peripheral nerve or main branches
Incidence - 2.5 - 5/100 000
Incidence after fracture (16 –46%)
Strain or sprain (10 –29%)
Post surgery (3 –24%)
Contusion or crush injury (8 –18%)
Upper limb : lower limb- 3: 2
Female : male ratio - 3: 2
Old > young (Common 50 – 60 yrs )
Multifactorial origin
Definitive cause still remains unknown
Three main hypotheses
Autonomic dysfunction
Neurogenic inflammation
Neuroplastic changes within the CNS
Increased Sympathetic activity
Upregulation of adregenic receptors
Adregenic receptor expression on nociceptive fibres
In chronic stage of CRPS
Acute tissue damage mediated classical inflammation
Cytokines – IL-1,IL-6 and TNF
Lowering pain threshold of nociceptive nerve endings
Peripheral sensitization
Neurogenic inflammatory response
Neuropeptides and cytokines released by nociceptors
Substance P, bradykinin and glutamate
Lower the pain threshold/ vasodilation/oedema
Peripheral sensitization
Early onset of distal odema – 80%
Changes / asymmetry skin colour - 40%
Initially red, becomes pale in chronic cases
Autonomic disturbances
Sensory changes
Motor disturbances
Trophic changes
Changes/ asymmetry skin temperature – 80%
Affected limb initially warm later become cold
Sudomotor changes
Hypohidrosis – Early diminished sweating
Hyperhydrosis - Increased sweating more common
Acute neuropathic pain - Stephan Schug - SSAI2017scanFOAM
A talk by Stephan Schug at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All of the conference content can be found here: https://scanfoam.org/ssai2017/
Developed in collaboration between scanFOAM, SSAI and SFAI.
Similar to CHRONIC PAIN AND DEPRESSION: Cause or Effect or Linked? (20)
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomSudhir Kumar
Neurological evaluation of acute ischemic stroke in ER should focus on:
1. Exclude stroke mimics
2. Ascertain time of onset of symptoms,
3. Neurological examination
4. NIHSS score
5. Investigations to be done in ER
6. Ascertain eligibility for thrombolysis and exclude any contraindications
7. Informed consent
Lifestyle Measures to Prevent Brain Diseases.pptxSudhir Kumar
Disease prevention is more important in neurology than treatment. This is because treatments are not 100% effective and cure may not be possible. In this presentation, I discuss the evidence-based measures to prevent stroke and dementia. These include adequate sleep, physical activity, eating healthy foods, and reducing stress.
This talk summarizes the definition, diagnosis and management strategies of migraine. It will be useful for general public as well as healthcare professionals.
This is more of a summary of recent evidence available on migraine management. It is easy to read and understand. Please post your queries and comments.
COVID-19 Presenting as stroke- mechanisms, diagnosis and treatmentSudhir Kumar
Covid 19 infection can affect nervous system in many ways, including an increased risk of stroke. This presentation looks at the association of COVID 19 infection and stroke. Mechanisms of stroke in COVID 19 have been elucidated. Approach to diagnosis and management has also been discussed via case studies. Prompt diagnosis and early initiation of treatment ensures a good outcome in covid 19 infected patients presenting with stroke.
Neurological Manifestations of COVID-19 InfectionSudhir Kumar
COVID-19 primarily affects respiratory system, however, it can affect other systems too, including nervous system. This presentation offers details about neurological symptoms and disorders seen in patients with COVID-19.
Zonisamide is among the newer broad spectrum anti-epileptic drugs, effective against focal and generalized epilepsies. It can be taken once daily and is well tolerated. The current article focuses on clinical efficacy and safety of zonisamide in epilepsy (as add on or as monotherapy). There is long term data as well as comparative studies against carbamazepine.
Multiple sclerosis: fighting the invisibleSudhir Kumar
Multiple sclerosis affects about 100 per 1,00,000 population. Women get affected 3 times more commonly than men. It is a leading cause of disability. This presentation aims at educating people with MS about the symptoms, diagnosis, treatment and prognosis of MS.
Stroke is common. This presentation discusses the broad outlines of acute stroke management, especially in the first 24 hours after onset of symptoms. It would be useful for physicians as well as neurologists.
Stroke is common in pregnancy. All physicians and obstetricians caring for pregnant women should be familiar with symptoms of stroke, as well as its diagnosis and treatment. This presentation gives an overview about the latest management of stroke in pregnant women.
Stroke is a leading cause of death and disability. All doctors should have a basic knowledge about stroke management. This presentation gives a summary of treatment options in acute brain stroke.
Multiple sclerosis is a demyelinating disease affecting brain, optic nerves and spinal cord. It is characterised by frequent relapses. Now, there are a number of effective treatment options for MS. Earlier, only clinical parameters were considered to evaluate the efficacy of MS treatments. However, now, we need to look at disability as well as MRI parameters. All these points are included in NEDA (no evidence of disease activity). This presentation looks at the definition and classification of NEDA. It also looks at NEDA rates with various treatment options.
NEUROLOGICAL DISORDERS DUE TO METABOLIC DERANGEMENTSSudhir Kumar
Metabolic and endocrine disorders can present with neurological signs and symptoms. It is important to recognise them so that can be promptly treated. Majority of symptoms fully reverse if treatment is started on time. This presentation looks at some common metabolic/endocrine disorders with neurological manifestations. The description is in the form of case series.
Management of High Disease Activity in Multiple Sclerosis (MS)Sudhir Kumar
Multiple sclerosis is a common disease affecting the central nervous system. Immunotherapy with interferon is the first line therapy for MS. This presentation discusses the treatment options of high disease activity in patients with MS. Role of natalizumab (tysabri) has been highlighted.
This presentation discusses the revised McDonald's criteria (2017) for the diagnosis of multiple sclerosis. Major changes from the last diagnostic criteria proposed in 2010 have been discussed. Clinical and MRI criteria for dissemination in space and time have been discussed.
Today, everyone needs to market self. Some market their products, and others market their skills. Is marketing difficult? It is difficult, however, it can become easy, if we follow certain protocol. This talk gives you some insights into effective ways of marketing.
Addressing hypertension to reduce the burden of stroke 19 feb2018 (1)Sudhir Kumar
Hypertension is the commonest risk factor for stroke. Management of hypertension is important in ensuring best outcomes for stroke patients. Adequate control of bP is also important to prevent stroke recurrence. This presentation looks at the role of high BP in stroke occurrence and antihypertensive agents that can be used to achieve target BP.
Role of Blood Pressure in Recurrent StrokeSudhir Kumar
Hypertension is a major risk factor for the first stroke as well as recurrent stroke. Therefore, adequate control of BP is necessary to reduce the risk of stroke recurrence. This presentation looks at the ABCD 2 score to predict the exact risk of stroke recurrence after TIA. Target BP that needs to be achieved has been discussed. Various antihypertensive agents based on the scientific evidence have been discussed.
Palmitoylethanolamide in the Treatment of Neuropathic Pain Sudhir Kumar
Neuropathic pain is quite common. It is associated with severe disability and adversely affects the quality of life of sufferers. Current treatment options for neuropathic are not very effective. Moreover, they are associated with significant adverse effects. A new naturally occurring substance- PALMITOYLETHANOLAMIDE (PEA)- has been found to be effective and safe in treating neuropathic pain. The current presentation looks at the efficacy of PEA in neuropathic pain.
Newer drugs for the treatment of motor symptoms of Parkinson's DiseaseSudhir Kumar
Parkinson's disease is a common movement disorder with prominent motor symptoms such as tremors, bradykinesia and rigidity. Many patients suffer from motor fluctuations including on off phenomena, and freezing. This presentation looks at the latest drugs for treating these.
Acute ischemic stroke is an emergency. There are good thrombolytic agents available now. Aspirin or clopidogrel along with statins should be given to all stroke patients. Control of BP and sugar is of paramount importance.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
CHRONIC PAIN AND DEPRESSION: Cause or Effect or Linked?
1. Chronic Pain & Depression
Management: The Hen & Egg
Conundrum
Dr Sudhir Kumar MD DM
Senior Consultant Neurologist
Apollo Hospitals, Hyderabad
2. Chronic Pain
• Pain- a subjective sensory and emotional experience.
• Chronic pain is any persistent or intermittent pain that lasts
more than 3 months.
• Major types
– Neuropathic: a lesion or disease involving the nervous system
– Nociceptive: a consequence of actual or threatened damage to
nonneural tissues
Neural Plasticity, vol. 2016, Article ID 6402942, 9 pages, 2016
Pain, vol. 156, no. 6, pp. 1003–1007, 2015.
8. Relation between Pain and Depression
• Both brain regions and the neurological function system, whereby chronic pain
may lead to depression
• Depression can cause pain — and pain can cause depression
• 85% of patients with chronic pain are affected by severe depression
• The biological basis for depression has focused on dysregulation of the
neurotransmitters serotonin (5-hydroxytryptamine, or 5-HT), norepinephrine (NE),
and dopamine.
• NE and 5-HT have been implicated in the underlying pathophysiology of chronic
pain
Archives of Internal Medicine, vol. 163, no. 20, pp. 2433– 2445, 2003.
Journal of Neurology, Neurosurgery, and Psychiatry, vol. 74, no. 11, pp. 1587–1589, 2003.
9. Pain and depression
Pain
• One fifth of the general population are affected
• Opioid receptor to relieve patients’ pain
• Opioids have been widely applied to treat various
chronic pains, such as cancer pain, nociceptive pain,
and neuropathic pain.
Depression
• Third leading contributor to the global disease
burden.
• Research suggest that there are three classical
types: μ, δ, and κ receptors, all of which involve in
regulating mood, and some potential mechanisms
have been studied.
• The combined effect of the μ receptor agonist and κ
receptor antagonist was found to have the potential
to reduce the occurrence of dysphoria like
behaviours
• Moreover, the κ receptor antagonist has been
indicated to have a possibly antidepressant effect
10. The neurotransmitters
• Serotonin (5-HT)
• Dopamine (DA)
• Norepinephrine (NE)
• Decreased availability: results in depression
• Vital to the occurrence and development of pain
Pharmacol Ther. 2015 Mar;147:1-11.
11. The neurotransmitters
• Chronic pain significantly damage DA activity in the limbic midbrain
area
• DA found reduced in chronic pain
• Inflammatory response has been shown to cause pain and
depression
• Inflammatory response-mediated pain may be more strongly
associated with depression
Journal of Neuroscience, vol. 35, no. 27, pp. 9957–9965, 2015.
Schizophrenia Research, vol. 118, no. 1–3, pp. 292–299, 2010.
12. The neurotransmitters
• Glutamate functions as one of the main excitatory neurotransmitters in
the CNS and exists in synapses throughout the brain
• Glutamate and its receptor subtypes, n-methyl d-aspartic acid (NMDA)
receptor and α-amino-3-hydroxy 5-methyl-4-isoxazolepropionic acid
(AMPA) receptor, have been found to be involved in the occurrence and
development of chronic pain and depression
Neural plasticity. 2017;2017.
13. The neurotransmitters
• Chronic pain and depression and may involve the same brain structures,
neurotransmitters, and signalling pathways
• Benzodiazepines used in treating chronic pains, including neuropathic pain
or inflammatory pain by antihyperalgesic effect of the GABAA
• GABAA receptors, including the α1, α2, α3, or α5 subunit, have also been
found to be involved in mood regulation.
• Benzodiazepines have a potential as antidepressant therapy.
• Benzodiazepines can potentially treat chronic pain-induced depression.
Neural plasticity. 2017;2017.
15. They may be connected…….
• Chronic Pain
• Patients with chronic pain are prone
to depression because of the
continuous disease burden imposed
by the pain.
• Because of the reciprocal nature of
depression and pain, the presence of
both conditions in a patient may lead
to an increased number of medical
visits as well as to higher health care
costs
• Depression
• Major depressive disorder (MDD) is a
multifaceted disease that presents
with both emotional symptoms (e.g.,
depression, guilt, suicidal ideation)
and physical symptoms (e.g., sleep
disruption, gastrointestinal
disturbance, unexplained aches and
pains).
• Headache, neck and back pain,
abdominal pain, and musculoskeletal
pain are common in patients with
depression
Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med. 2003;163:2433-2445.
16. TCA as “Double Duty” drugs
• TCAs are the Drugs used for depression, found
effective also for chronic pain as reported in
many studies. Hence commonly used in both.
Micó J, Ardid D, Berrocoso E, Eschalier A (2006). "Antidepressants and pain". Trends Pharmacol Sci. 27 (7): 348–54
17. Mechanism
• Their main mechanism of action involves
– reinforcement of the descending inhibitory pathways by increasing
the amount of norepinephrine and serotonin in the synaptic cleft at
both supraspinal and spinal levels.
• The analgesic effect occurs
– In the absence of depression or where there was no antidepressant
effect
– At doses lower than those used for depression
– With an earlier onset of effect (i.e., within 1 week) than that required
for an antidepressant effect.
J Psychiatry Neurosci 2001;26(i):30-6. 17
18. MECHANISM OF ACTION OF ANTIDEPRESSANTS AS ANALGESICS
Mechanism of action Site of action TCA SNRI SSRI
1.Reuptake inhibition of monoamine Serotonin, Noradrenaline +
+
+
+
+
-
2.Receptor antagonism Adrenaline(alpha 1) NMDA +
+
-
+milnacipran
-
-
3.Blocker or Activation of ion channel Sodium channel blocker + +venlafaxine +fluoxetine
Calcium channel blocker + -duloxetine
Potassium channel blocker + ?
4.Adenosine Increase adenosine availability and
local release, activation of adenosine
A1 receptors
+amitriptyline ? ?
5.GABA b receptors Increase GABA b receptor function +amitriptyline
desipramine
? +fluoxetine
6.Opiod receptor binding/opioid mediated
effect
Activation of ƍ and ũ opioid receptors + +venlafaxine +paroxetine
7.Inflammation Decrease PGE2 production + ? +fluoxetine
Decrease TNF α production + ? ?
J clinical pharmacol 2012:52,6,17-
18
19. TCAs FOR PAIN
• TCAs should be initiated at low dosages—10 to 25 mg in a single dose at
bedtime—and then titrated every 3 to 7 days by 10 to 25 mg/d as
tolerated
• TCAs should be titrated to maximum dosages of 75 to 150 mg/d as
tolerated
• TCA treatment should last 6 to 8 weeks, with at least 1 to 2 weeks being at
the maximum tolerated dosage.
19
20. NEUROPATHIC PAIN
• Neuropathic pain is defined by the International Association for the Study
of Pain (IASP) as ‘pain caused by a lesion or disease of the somatosensory
nervous system.
• Around 7–8% of adults have pain with neuropathic characteristics.
• Most common cause of neuropathic pain are
• Diabetic neuropathy(25%)
• HIV associated sensory peripheral neuropathy(35%)
• Chemotherapy induced peripheral neuropathy
• Postherpetic neuralgia(19%)
• Trigeminal neuralgia
• Postsurgical pain(10%)
20
21. NEUROPATHIC PAIN
• Tricyclic antidepressants (TCAs) are the “gold standard”
antidepressants for the treatment of persistent
neuropathic pain.
• TCAs along with SNRIs and gabapentinoids are first line
therapy. 3
• TCAs are one of the most studied antidepressants for the
treatment of neuropathic pain.
• Their use as a first-line therapy is supported across
multiple guidelines 3
1. Drugs Aging. 1996; 8: 459
2. Neurology. 1995; 45( Suppl 9): 17– 25.
3.Pain Med2019 Jun ; 20(Suppl 1): S2–S12.
21
22. FIBROMYALGIA
• Efficacy of TCAs is well-established in fibromyalgia.
• Amitriptyline has long been used in pharmacological treatment.1
• TCAs are effective at doses lower than those needed for the
treatment of depression.2
• A meta-analysis by Arnold et al included 9 RCTs with TCAs
(amitriptyline, dosulepin) in fibromyalgia patients observed.3
– 30% patients showed improvement in all outcomes (fatigue, sleep,
pain,stiffness, tenderness)
– A greater effect was seen on sleep disorders and fatigue than on pain,
indicating that TCAs had a moderate analgesic effect in fibromyalgia.
1 .Biomedicines 2017 Jun; 5(2): 20.
2. J Musculoskel Pain. 1996;4:37-47.
3.Psychosomatics. 2000;41:104-113 22
23. OTHER CHRONIC PAIN CONDITIONS
Low back pain
• According to American Pain Society and
American College of Physicians
guidelines, TCAs are effective for pain
relief in LBP.1
• Their analgesic effect has been reported
to be similar to that of NSAIDs.2
• A meta analysis revealed that
antidepressants had a statistically
significant effect in reducing LBP when
compared with placebo. Patients treated
with antidepressants experienced a small
but significant improvement of 0.41 (95%
CI 0.22–0.61) in the standardized mean
difference for pain severity.3
Chronic headache
• Meta-analyses have demonstrated that
patients receiving antidepressants were
twice as likely to report headache
improvement (rate ratio [RR]: 2.0; 95%
CI: 1.6 to 2.4.94–96 The beneficial effect
of TCAs was the largest of all
antidepressants.
1. Ann Intern Med. 2007;147:505-514.
2. Pain Symptom Manage. 2004;28:72-95.
3. Arch Intern Med. 2002;162:19-24.
Am J Med. 2001;111:54-63.
23
24. RHEUMATOID ARTHRITIS
• TCAs have only weak analgesic effects in patients with RA, with or without depressive
symptoms.1
• In a study of 123 RA patients with anxiety/depression, patients treated with
DMARDs+antidepressants achieved remission significantly more often (p=0.024) than
ones receiving DMARDs only. Thus, successful treatment of depression/anxiety with
antidepressants provided more significant positive influence on treatment response to
DMARDs and biologics on a five-year follow-up.2
• A Cochrane review(2011) concluded that3
– There is currently insufficient evidence to support the routine prescription of
antidepressants as analgesics in patients with RA as no reliable conclusions about
their efficacy can be drawn from eight placebo RCTs.
1.Rheumatology 2008;47:1117–1123
2.Annals of rheumatic disease ,vol 77,supp 2
3.Cocrane database syst rev 2011 Nov 9;(11 24
25. Benefits of TCA in Pain and Depression
Pain Depression
TCAs are the most studied
antidepressants for the treatment of
neuropathic pain
People with severe depression that fail to
respond to other treatments. TCAs are
effective
Reduce pain in lowered doses as compare
to depression
108 studies of newer antidepressants that
found TCAs to be effective in treating
depression.
Br Med Bull. 2001;57:161–178
26. Less Number Needed to treat (NNT) of TCAs
• In a Cochrane review of 61 RCTs, it was found that TCAs had 4
– A number needed to treat (NNT) of 3.6 for the achievement of
moderate pain relief
– A number needed to harm (NNH) for adverse effects, defined as
an event leading to withdrawal from a study, of 28.
– For minor adverse effects, the NNH was 9.
Cochrane Database Syst Rev 2007;4: CD005454
27. Dosulepin a Safe TCA
• Dosulepin, also known as dothiepin is a tricyclic antidepressant.
• It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has
other actions including anti-histaminic, anti-adrenergic, anti-serotonergic, anti-
cholinergic, and sodium channel blocking effects.
• Indication
– Dosulepin is licensed for the treatment of depressive illness in adults along with
chronic pain or anxiety
Contraindication
– Recent myocardial infarction
– Heart block of any degree or other cardiac arrhythmias
– Mania
– Severe liver disease
27
PrescQIPP DROP-List. Bulletin available at www.prescqipp.info
28. Dothiepin Vs Amitriptyline
• 23 independent studies performed in 8 countries over an 18-year period
between 1971 and 1988 in over 1000 evaluable patients indicates that
dothiepin is as effective as amitriptyline but is better tolerated
Donovan, S., Vlottes, P.W. & Min, J.M. Drug Invest. (1991) 3: 178. https://doi.org/10.1007/BF03259561
D=Dothiepin
A=Amitriptyline
29. • Dothiepin Versus Amitriptyline for Depression An Analysis of Comparative Studies1
– Dothiepin is equally effective as amitriptyline and better tolerated
– Consistent pattern of findings in these studies suggests - dothiepin is better than amitriptyline in the
treatment of depression
• A Double-Blind Study of Dothiepin Hydrochloride and Amitriptyline in Out-Patients with Masked
Depression2
– Frequency and severity of side-effects like hypotension, tiredness/sleepiness and dry mouth -
significantly less with dothiepin than with amitriptyline at Week 1 (p <0·05)
– The overall incidence and severity of side-effects was also less with dothiepin at all assessments during
the trial
• Single-blind comparative study of once daily dothiepin and divided daily doses of amitriptyline3
– Dothiepin caused a greater improvement than amitriptyline after 4 weeks of treatment - judged
by depression scores, total scores and global assessments
– The incidence of side-effects was less in number and severity with dothiepin than with
amitriptyline
1.Donovan et al. Dothiepin Versus Amitriptyline for Depression An Analysis of Comparative Studies. Drug Invest. 3 (3): 178-182, 1991 01 14-2402/91/0003-01 78.
2.Dahl et al. A Double-Blind Study of Dothiepin Hydrochloride (Prothiaden) and Amitriptyline in Out-Patients with Masked Depression. Int Med Res (1981) 9,103
3. Rees et al. A single-blind comparative study of once daily dothiepin (‘Prothiaden’) and divided daily doses of amitriptyline. Cum. Med. Res. Opin., (1976),4,416.
Dosulepin or Amitriptyline – Which is a better choice?
Dosulepin (Dothiepin) is a safer and equally effective alternative to Amitriptyline
30. Proprietary and confidential — do not distribute 30
SSRI vs Dosulepin – which has got better tolerability?
SSRI treatment results in more side-effect related drop outs compared to Dosulepin
31. Conclusion
• Chronic pain and depression are probably linked to each other as they share the
common pathways on neurotransmission
• Depressed patients may have both neuropathic and nociceptive pain
• Alternatively, patients in chronic pain may have some level of depression
• TCA are safe, cost-effective agents that are useful in both conditions
• In depression with pain – TCAs should be preferred
• Dosulepin may prove to be a useful treatment option for patients of Chronic pain
with Depression or anxiety
Pathogenesis of acute and chronic pain. Stage I: Acute pain is associated with inflammation and activation of spinal pathways that send instructive pain messages to encourage future injury avoidance and cause protective muscle spasm. Stage II: Over ensuing weeks, injured tissues heal, inflammation resolves, and fewer central impulses are sent that can be registered as pain or trigger muscle spasm. Stage III: In patients who develop chronic pain, the nervous system continues to send signals for pain and muscle spasm as though in response to an acute injury, even though the injury is only a memory. Therefore, someone with chronic lumbar pain who is sitting in a chair may receive useless information that he or she is being injured and experience pain and muscle spasm, even though no active injury is present.
Pathogenesis of chronic pain. Normally, stimulation of tactile receptors activates the dorsal column pathway and activation of free nerve endings activates the lateral spinothalamic pain pathway. Painful stimuli that are active during acute pain increase the signaling rate within the lateral spinothalamic pain pathway. Physiological changes occurring during chronic pain result in stimulation of tactile receptors (e.g., touch or vibration) activating lateral spinothalamic pathways, which results in the false interpretation by the brain that pain-sensitive nerve endings have been activated.