ROLE OF INFLAMMATION IN PSYCHIATRIC DISORDERS

Dr MUHAMMAD HARIS BURKI  MBBS,PhD ( harisburki@yahoo.com)

ZUBAIR MUKHTAR Msc psychology

JAWAD SHUJJAT Msc psychology

 

 

INTRODUCTION AND

DISCUSSION

Presently psychiatry relies heavily on dysfunction in endogenous monoamine system hypotheses.  Pathophysiogy of depression, anxiety, bipolar, schizophrenia is explained on bases of disturbance of neurotransmitters .Available treatments in psychiatry have not been successful in restoring normal functionality. Inflammatory products like cytokines have been implicated in pathophysiology of psychiatric disorders. Cytokines can modify neurotransmitters, neural and glial plasticity across BBB. Greater incidences of inflammatory disease like cardiovascular and autoimmune diseases and increased incidence of psychiatric  co morbidity like depression in inflammatory disease like ankylosing spondylitis, rheumatoid arthritis psoriasis. Patient treated with interferon are at greater risk of having psychiatric illness. Bilateral relation between psychiatric and inflammatory disease suggest common underlying pathophysilogical process is at work. Inflammatory mediators like IL-6,IL2, TNFalpha  CRP are implicated in pathphysiology of psychiatric illness.Oxidative stress is closely related to the inflammation .Oxidative stress effect methylation of DNA causing increase susceptibility of psychiatric disorder. Homocystine level are increased in various inflammatory diseases.It is found elevated in in various psychiatric illness like depression.addiction,and etc.

 

Chronic inflammation may act as catalyst in different form of addction.Inflammation precedes in preponderant majority of addiction patient.Increase o glutametergic tonus and decrease of  dopaminergic neurotransmission in nucleus accumben  and hypothalamus.

 

Role of anti-inflammatory is currently being investigated as treatment option in psychiatric diseases. Among these are included celecoxibs  ,minocycline,Nacetyle cystine are important. Homocystine lowering food supplement like methyl folate.B6,B12 ,Bethian .SAMe has shown good results in resistant cases of depression.

N accetyle cystine is currently used as mucolyting agent. It is precursors of glutathione, and has anti-inflammatory, antioxidant, homocystine reducing ,antiglumatergic  and dopaminergic modulatinga properties. It has role in treatment of different type of  addictions, bipolar disorder, schizophrenia , grooming disorder and OCD. Oxidative stress is cumulative interactional effect of all pathways. Standard treatment has shown limited efficacy in these disorders. N acetyle has emerged as promising adjuvant agent in treatment of psychiatric disorders. This novel agent has opened vistas of novel hypothesis based therapies in field of psychiatry.

CONCLUSION:

There may be different psychopathogies of various psychiatric disorders. Chronic Inflammation is may be a triggering factors which acts on the genetic predisposition or may be aggravating factor of disease. This description is reminiscent of unitary psychosis. Treatment with anti-inflammatory and antioxidant can alleviate psychiatric symptoms. It like antipyretic medication can lower down fever what ever is underlying cause.

TREATMENT OF SEXUAL DYSFUNCTION AND OCD : A PARADOX

DR MUHAMMAD HARIS BURKI (MBBS,PhD) harisburki@yahoo.com

PROF  KHALEEQ –UR- RAHMAN (FRCS FCSM)

 

INTRODUCTION:

There is high prevalence of sexual dysfunction in drug naïve OCD patients. They tend to have greater orgasmic and erectile difficulties. 50% of OCD patients have sexual dysfunction. Between  60% to 73%  have dissatisfied sexual lives. Anorgasmia was found in 24.2%  and sexual avoidance in 60.6%of OCD female patients.

SSRI, s used for treatment of OCD further impair sexual functions. It induces lack of libido, orgasmic difficulty and erection and lubrication problems. This class of drug reduces dopamernergic transmission at meso limbic circuit and increase of prolactin level which has dampening effect on sexual function. It also cause desensitization of erotogenic zones of body.  Sexual dysfunction is reported in 80% of SSRI,s treated patients.

There are pharmacological    and psychological options.  Strategies we can use are psychotherapy, drugs with minimum SD, and add drugs to undo sexual side effects.  CBT can be used for treatment of OCD which can pass by SSRI,s. Simultaneously sex therapy can be used including CBT, masturbation, mindfulness techniques.  Concomitant treatment of OCD and sexual dysfunction is a challenging task.

In pharmacological treatment we can adopt two strategies

MEDICATION THAT CAN LOWER OCD SCORES WITH MINIMUM SEXUAL SIDE EFFECTS
ADD ON MEDICATION TO UNDO SEXUAL SIDE EFFECTS

 MIANSERIN  and MIRTAZEPINE

Miaserin can be given to stabilized OCD patient. When mianserin was added to female patients there was no change in OCD symptoms .However undesirable sexual side effect were greatly reduced. Study on male patient has shown similar results of reversing   SSRI induced sexual side effects.

When mirtazepine is added to citalopram for treatment of there was early onset of response along with reduction of sexual side effect. Mirtazepine has antagonist effect on 5HT2A/5HT2C/5HT3 and alpha 2 receptors.

 ANTI GLUTAMETERGIC MEDICINE

KETAMINE

Glutamine play important role in patho physiology of OCD. Randomized trail show efficacy of ketamine which is a non competitive NMDA receptor antagonist. It could achieve rapid anti obsessional   effect without involvement of serotonergic system.

MEMENTINE

Drug used in treatment of dementia belong to NMDA receptor antagonist. When added to fluvoxamine improved outcome of OCD treatment without additional side effects. Memtentine can help reduce dose of SSRI which would improve sexual function.

LAMOTRIGINE

Used as antiepileptic and mood stabilizer can be used as augmentation therapy for resistant OCD. Lamotrigine has few sexual side effect can help I dose reduction of SSRI,s in OCD patients.

VILAZEDONE

Vilazedone is has combine properties of SSRI and partial agonist of pre and post synaptic 5HT1A.It has minimum sexual side effect because 5HT1A can modify dopamine transmission .Agonism of this receptor can decrease inhibitory effect on dopamine release.

Modification of 5HT receptor can modulate glutamate transmission via 5HT1A ,5HT1B,5HT3,5HT7.It is possible to use combination of drugs to enhance anti OCD with out additional sexual side effects.

N acetyle cystine

N acetyle cystine can augment antiobsessional effect SSRI.This particular molecule has prosexual  central and peripheral effect. It has anti oxidant, anti inflammatory, dopamenergic , anti glutamertegic and homocystien lowering properties. Combine effect improves vascular health through endothelial function. Central effect help improve neurotransmitter synthesis.

PDE5 inhibitor

Although PDE5I don,t have no role  to play in CNS function. Yet can help OCD patients. Due to their safe and potent effect on arousal can counter sexual side effect of SSRI,s. This improves compliance of medication. Improved sexual function helps improve mood and add to general well being of patient.

CONCLUSION:

For comprehensive treatment of OCD treatment sexual function need to be addressed properly. So many time sexologist find obsessive patient presenting with sexual symptom. So both sexologist and psychiatrist have to evolve strategy to deals two separate problems concomitantly.

TREATMENT OF SEXUAL DYSFUNCTION AND OCD : A PARADOX

DR MUHAMMAD HARIS BURKI (MBBS,PhD) harisburki@yahoo.com

PROF  KHALEEQ –UR- RAHMAN (FRCS FCSM)

 

INTRODUCTION:

There is high prevalence of sexual dysfunction in drug naïve OCD patients. They tend to have greater orgasmic and erectile difficulties. 50% of OCD patients have sexual dysfunction. Between  60% to 73%  have dissatisfied sexual lives. Anorgasmia was found in 24.2%  and sexual avoidance in 60.6%of OCD female patients.

SSRI, s used for treatment of OCD further impair sexual functions. It induces lack of libido, orgasmic difficulty and erection and lubrication problems. This class of drug reduces dopamernergic transmission at meso limbic circuit and increase of prolactin level which has dampening effect on sexual function. It also cause desensitization of erotogenic zones of body.  Sexual dysfunction is reported in 80% of SSRI,s treated patients.

There are pharmacological    and psychological options.  Strategies we can use are psychotherapy, drugs with minimum SD, and add drugs to undo sexual side effects.  CBT can be used for treatment of OCD which can pass by SSRI,s. Simultaneously sex therapy can be used including CBT, masturbation, mindfulness techniques.  Concomitant treatment of OCD and sexual dysfunction is a challenging task.

In pharmacological treatment we can adopt two strategies

MEDICATION THAT CAN LOWER OCD SCORES WITH MINIMUM SEXUAL SIDE EFFECTS
ADD ON MEDICATION TO UNDO SEXUAL SIDE EFFECTS

 MIANSERIN  and MIRTAZEPINE

Miaserin can be given to stabilized OCD patient. When mianserin was added to female patients there was no change in OCD symptoms .However undesirable sexual side effect were greatly reduced. Study on male patient has shown similar results of reversing   SSRI induced sexual side effects.

When mirtazepine is added to citalopram for treatment of there was early onset of response along with reduction of sexual side effect. Mirtazepine has antagonist effect on 5HT2A/5HT2C/5HT3 and alpha 2 receptors.

 ANTI GLUTAMETERGIC MEDICINE

KETAMINE

Glutamine play important role in patho physiology of OCD. Randomized trail show efficacy of ketamine which is a non competitive NMDA receptor antagonist. It could achieve rapid anti obsessional   effect without involvement of serotonergic system.

MEMENTINE

Drug used in treatment of dementia belong to NMDA receptor antagonist. When added to fluvoxamine improved outcome of OCD treatment without additional side effects. Memtentine can help reduce dose of SSRI which would improve sexual function.

LAMOTRIGINE

Used as antiepileptic and mood stabilizer can be used as augmentation therapy for resistant OCD. Lamotrigine has few sexual side effect can help I dose reduction of SSRI,s in OCD patients.

VILAZEDONE

Vilazedone is has combine properties of SSRI and partial agonist of pre and post synaptic 5HT1A.It has minimum sexual side effect because 5HT1A can modify dopamine transmission .Agonism of this receptor can decrease inhibitory effect on dopamine release.

Modification of 5HT receptor can modulate glutamate transmission via 5HT1A ,5HT1B,5HT3,5HT7.It is possible to use combination of drugs to enhance anti OCD with out additional sexual side effects.

N acetyle cystine

N acetyle cystine can augment antiobsessional effect SSRI.This particular molecule has prosexual  central and peripheral effect. It has anti oxidant, anti inflammatory, dopamenergic , anti glutamertegic and homocystien lowering properties. Combine effect improves vascular health through endothelial function. Central effect help improve neurotransmitter synthesis.

PDE5 inhibitor

Although PDE5I don,t have no role  to play in CNS function. Yet can help OCD patients. Due to their safe and potent effect on arousal can counter sexual side effect of SSRI,s. This improves compliance of medication. Improved sexual function helps improve mood and add to general well being of patient.

CONCLUSION:

For comprehensive treatment of OCD treatment sexual function need to be addressed properly. So many time sexologist find obsessive patient presenting with sexual symptom. So both sexologist and psychiatrist have to evolve strategy to deals two separate problems concomitantly.

USE OF GABAPENTINE IN SOMATIC BURNING SENSATION IN ANXIO DEPRESSED POST MANOPAUSAL WOMEN

MUHAMMAD HARIS BURKI

HAROON RASHID

MIRAT GUL

 

INTRODUCTION:

 

Gabapentine has broad spectrum of usage. It has been tried in epilepsies, neuropathies, chronic pains, migraine prophylaxis movement disorders, muscular spasm, sleep disorder and anxiety.It has been used in diabetic neuropathies and nondiabetic neuropaties.For treatment of prophylaxis of migraine. For treatment of fibromyalgia ,muscular spasm and pain associated with spinal cord injury and priaprism .It has used for treatmet of essential tremor ,restless leg syndrome and nystagmus..Mix anxiety depression is highly prevalent among post menopausal ladies. Postmenopausal symptoms include mood swings, irritability ,lack of concentration, change of  sleep and appetite pattern, diminished vaginal secretion, and hot flushes .Feelings of warmth, profuse perspiration, and itching of skin may be part of hot flushes. Many features of  post menopausal  syndrome cannot be separated from  typical mix anxiety and depression. SSRI,s are used for both PMS and mix anxiety depression syndrome.

OBJECTIVES:

To evaluate efficacy of gabapentine in the symptom of burning sensation in the body in anxio depressed postmenopausal women.

METHOD:

Ten postmenopausal anxio depressed  patients having severe compliant of burning sensation in the body treated with standard regime of SSRI,s and benzodiazepines. Symptoms of anxiety and depression responded well .However ,burning sensation remained unabated. These patients were started 100mg gabapentine tid which was later increased to   300mg tid.

RESULTS :

There was substantial reduction in feeling of burning sensation in all the patients. Besides concomitant reduction in anxiety ,muscular pains and aches and improvement in sleep.

DISCUSSION:

Gabapentine has gabanergic and antiglutametergic properties. It interacts with 2 subunits of voltage dependent calcium channels. Central analgesic effect of gabapentine is mediated both by suraspinal and spinal action involving descending nonadrenergic system. Intra cerebroventrical administration decrease thermal mechanical hypersensitivity .This supraspinal effect is independent of spinal cholinergic –NO system. Pretreatment with yohimbine abolishes beneficial effects. In hot flushes action on noradrenergic system and property of reducing thermal hypersensitivity of gabapentine might have been helpful. Effect on the alpha 2 receptors is probably gapentine effect  on autonomic nervous system involved in hot flushes. Gabapentine has not very good effect in treatment of hot flushes in  breast cancer treatment. Instead SSRI,s has given better results .In this study gabapentine was added adjunt to SSRI,s and possibilly in anxio depressed patient its sedative ,anti anxiety, and muscle relaxant properties might have played some role. Similar study could done on male patients with andropause.