ANXIETY DISORDERS & MANAGEMENT

ANXIETY DISORDERS

SILCHAR MEDICAL COLLEGE & HOSPITAL

PLAN OF PRESENTATION

• INTRODUCTION

• TYPES OF ANXIETY

• NEUROBIOLOGY OF ANXIETY DISORDERS

• SYMPTOMATOLOGY

• MANAGEMENT• PHARMACOLOGICAL

• NON PHARMACOLOGICAL

• RECENT ADVANCES

WHAT IS ANXIETY ?

• ANXIETY IS A DIFFUSE, HIGHLY UNPLEASANT, OFTEN VAGUE FEELING OF APREHENSION, ACCOMPANIED BY ONE OR MORE BODILY SENSATIONS-PALPITATIONS, PERSPIRATIONS, HEADACHE ETC.

• PHILOSOPHERS AND THINKERS HAVE LONG WRITTEN ABOUT THE CENTRALITY OF ANXIETY IN HUMAN LIFE AND EXPERIENCES.

• ON THE OTHERHAND, IT IS ONE OF THE NEWEST OF SUBJECTS AS THE SCIENTISTS ARE UNDERSTANDING THE UNDERLYING PSYCHOBIOLOGY AND ITS MANAGEMENT, EFFECTIVELY ONLY FOR LAST FEW DECADES.

DEFINITION

“Feeling of apprehension caused by anticipation of danger, which may be internal or external”

“Anxiety is an emotional state commonly caused by the perception of real or perceived danger that threatens the security of an individual. It allows a person to prepare for or react to environmental changes.”

• This is an adaptive response, and is transient in nature.

• ANXIETY IS A NORMAL EMOTION UNDER CIRCUMSTANCES OF THREAT AND IS THOUGHT TO BE PART OF THE EVOLUTIONARY “FIGHT OR FLIGHT” REACTION OF SURVIVAL.

• ANXIETY CAN PRODUCE UNCOMFORTABLE AND POTENTIALLY DEBILITATING PSYCHOLOGICAL (E.G., WORRY OR FEELING OF THREAT) AND PHYSIOLOGICAL AROUSAL (E.G., TACHYCARDIA OR SHORTNESS OF BREATH) IF IT BECOMES EXCESSIVE.

• SOME INDIVIDUALS EXPERIENCE PERSISTENT, SEVERE ANXIETY SYMPTOMS AND POSSESS IRRATIONAL FEARS THAT SIGNIFICANTLY IMPAIR NORMAL DAILY FUNCTIONING.

• THESE PERSONS OFTEN SUFFER FROM AN ANXIETY DISORDER.

TYPES OF ANXIETY

• AN INTEGRAL PART OF OUR DAY TO DAY LIFE AND HELPS THE INDIVIDUAL IN COPING WITH STRESS DEVELOPING • BETTER ADAPTIVE SKILL• PLANNING AHEAD• BETTER PERFORMANCE

• INTENSED INTERNAL UNCOMFORTABLE FEELING STATE LEADS TO MALADAPTIVE BEHAVIOUR, THOUGHT AND COGNITONS AND POORER PERFORMANCE.

NORMAL ANXIETY PATHOLOGICAL ANXIETY

ANXIETY DISORDER

CLASSIFICATION OF ANXIETY DISORDER

• PANIC DISORDER WITHOUT AGORAPHOBIA.

• PANIC DISORDER WITH AGORAPHOBIA.

• AGORAPHOBIA WITHOUT H/O PANIC DISORDER.

• SPECIFIC PHOBIA.

• SOCIAL PHOBIA.

• OCD

• PTSD

• ACUTE STRESS DISORDER

• GENERALISED ANX- DISORDER.

• ANXIETY DISORDER DUE TO

• GENERAL MEDICAL CONDITION.

• SUBSTANCE INDUCED ANXIETY DISORDER.

• ANXIETY DIS ORDER NOS.

• SEPARATION ANXIETY DISORDER

• SELECTIVE MUTISM

• SPECIFIC PHOBIA

• SOCIAL ANXIETY DISORDER

• PANIC DISORDER

• PANIC ATTACK

• AGORAPHOBIA

• GENERELIZED ANXIETY DISORDER

• SUBSTANCE/MEDICATION INDUCED ANXIETY DISORDER

• ANXIETY DISORDER DUE TO ANOTHER MEDICAL CONDITION

• OTHER SPECIFIED ANXIETY DISORDER

• UNSPECIFIED ANXIETY DISORDER

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NEUROBIOLOGY OF ANXIETY DISORDERS

ALL ANXIETY DISORDERS HAVE 2 COMPONENTS

TO UNDERSTAND THE NEUROBIOLOGY OF ANY ANXIETY DISORDER WE NEED TO UNDERSTAND THE NEUROBIOLOGY OF BOTH

FEAR

WORRY

FEAR- PANIC- PHOBIA

WORRY- ANXIOUS MISERY- APPREHENSION - EXPECTATION- OBSESSIONS

LINKING ANXIETY SYMPTOMS TO CIRCUITS

ANXIETY AND FEAR SYMPTOMS ARE REGULATED BY AN AMYGDALA-CENTERED CIRCUIT.

WORRY, ON THE OTHER HAND, IS REGULATED BY A CORTICO-STRIATO-THALAMOCORTICAL (CSTC) LOOP.

THESE CIRCUITS MAY BE INVOLVED IN ALL ANXIETY DISORDERS, WITH THE DIFFERENT PHENOTYPES REFLECTING NOT UNIQUE CIRCUITRY BUT RATHER DIVERGENT MALFUNCTIONING WITHIN THOSE CIRCUITS.

LOOKING AFRAID/ AFFECT OF FEAR

AMYGDALA

ORBITO FC

ACC

• FEELINGS OF FEAR ARE REGULATED BY RECIPROCAL CONNECTIONS BETWEEN THE AMYGDALA AND THE ANTERIOR CINGULATE CORTEX (ACC) AND THE AMYGDALA AND THE ORBITOFRONTAL CORTEX (OFC).

• SPECIFICALLY, IT MAY BE THAT OVER ACTIVATION OF THESE CIRCUITS PRODUCES FEELINGS OF FEAR.

WHAT YOUWILL DO ?

FIGHT !FLIGHT !FREEZE !

AVOIDANCE/FIGHT/FLIGHT/FREEZE MOTOR RESPONSE

AMYGDALA

PAG

• FEELINGS OF FEAR MAY BE EXPRESSED THROUGH BEHAVIORS SUCH AS AVOIDANCE, WHICH IS PARTLY REGULATED BY RECIPROCAL CONNECTIONS BETWEEN THE AMYGDALA AND THE PERIAQUEDUCTAL GRAY (PAG).

• AVOIDANCE IN THIS SENSE IS A MOTOR RESPONSE.

• OTHER MOTOR RESPONSES ARE TO FIGHT OR TO RUN AWAY (FLIGHT) IN ORDER TO SURVIVE THREATS FROM THE ENVIRONMENT.

HYPERVENTILATION

CHANGES IN RESPIRATORY RATE

AMYGDALA

PBN

• CHANGES IN RESPIRATION MAY OCCUR DURING A FEAR RESPONSE; THESE CHANGES ARE REGULATED BY ACTIVATION OF THE PARABRACHIAL NUCLEUS (PBN) VIA THE AMYGDALA.

• INAPPROPRIATE OR EXCESSIVE ACTIVATION OF THE PBN CAN LEAD NOT ONLY TO INCREASES IN THE RATE OF RESPIRATION BUT ALSO VARIOUS SYMPTOMS.

SHORTNESS OF BREATH EXACERBATION OF ASTHMA, OR A SENSE OF BEING SMOTHERED.

AUTONOMIC OUTPUT OF FEAR

SUDDEN DEATH

ATHEROSCLEROSISCARDIAC ISCHEMIABLOOD PRESSUREMYOCARDIAL INFARCTION

“SCARED TO DEATH” MAY NOT ALWAYS BE AN EXAGGERATION OR A FIGURE OF SPEECH!

AUTONOMIC OUTPUT OF FEAR

AMYGDALA

LC

• AUTONOMIC RESPONSES ARE TYPICALLY ASSOCIATED WITH FEELINGS OF FEAR.

• THESE INCLUDE INCREASES IN HEART RATE (HR) AND BLOOD PRESSURE (BP), WHICH ARE REGULATED BY RECIPROCAL CONNECTIONS BETWEEN THE AMYGDALA AND THE LOCUS COERULEUS (LC).

• LONG-TERM ACTIVATION OF THIS CIRCUIT MAY LEAD TO INCREASED RISK OF ATHEROSCLEROSIS, CARDIAC ISCHEMIA, CHANGE IN BP, DECREASED HR VARIABILITY, MYOCARDIAL INFARCTION (MI), OR EVEN SUDDEN DEATH.

ENDOCRINE OUTPUT OF FEAR

ENDOCRINE OUTPUT OF FEAR

AMYGDALA

HYPOTHALAMUS

• THE FEAR RESPONSE MAY BE CHARACTERIZED IN PART BY ENDOCRINE EFFECTS SUCH AS INCREASES IN CORTISOL, WHICH OCCUR BECAUSE OF AMYGDALA ACTIVATION OF THE HYPOTHALAMIC–PITUITARY–ADRENAL (HPA) AXIS.

• PROLONGED HPA ACTIVATION AND CORTISOL RELEASE CAN HAVE SIGNIFICANT HEALTH IMPLICATIONS, SUCH AS INCREASED RISK OF CORONARY ARTERY DISEASE, TYPE 2 DIABETES, AND STROKE.

STRESS AND THE HPA AXIS

ADULT STRESSORS

DISINHIBITIONOF HPA AXIS BY HIPPOCAMPUS

CRFRELEASE

ACTH RELEASE

GLUCO-CORTICOID

RELEASE

HIPPOCAMPALATROPHY

ABNORMAL STRESS RESPONSE

MDD ANXIETY DISORDER

CRFRELEASE

GLUCOCORTICOIDSINHIBIT CRF

RELEASE

ACTH RELEASE

GLUCO-CORTICOID

RELEASE

NORMAL STRESS RESPONSE

PATHOPHYSIOLOGY

• DATA FROM BIOCHEMICAL AND NEUROIMAGING STUDIES INDICATE THAT THE MODULATION OF NORMAL AND PATHOLOGIC ANXIETY STATES IS ASSOCIATED WITH MULTIPLE REGIONS OF THE BRAIN AND ABNORMAL FUNCTION IN SEVERAL NEUROTRANSMITTER SYSTEMS, INCLUDING

• NOREPINEPHRINE (NE)

• SEROTONIN (5-HT)

• γ –AMINOBUTYRIC ACID (GABA)

NORADRENERGIC MODEL

• THIS MODEL SUGGESTS THAT THE AUTONOMIC NERVOUS SYSTEM OF ANXIOUS PATIENTS IS HYPERSENSITIVE AND OVERREACTS TO VARIOUS STIMULI.

• THE LOCUS CERULEUS MAY HAVE A ROLE IN REGULATING ANXIETY, AS IT ACTIVATES NOREPINEPHRINE RELEASE AND STIMULATES THE SYMPATHETIC AND PARASYMPATHETIC NERVOUS SYSTEMS.

5-HT MODEL

• GAD SYMPTOMS MAY REFLECT EXCESSIVE 5-HT TRANSMISSION OR OVERACTIVITY OF THE STIMULATORY 5-HT PATHWAYS.

• PATIENTS WITH SAD HAVE GREATER PROLACTIN RESPONSE TO BUSPIRONE CHALLENGE, INDICATING AN ENHANCED CENTRAL SEROTONERGIC RESPONSE.

• THE ROLE OF 5-HT IN PANIC DISORDER IS UNCLEAR, BUT IT MAY HAVE A ROLE IN DEVELOPMENT OF ANTICIPATORY ANXIETY.

• PRELIMINARY DATA SUGGEST THAT THE 5-HT AND 5-HT2 ANTAGONIST METACHLOROPHENYLPIPERAZINE CAUSES INCREASED ANXIETY IN PTSD PATIENTS.

γ-AMINOBUTYRIC ACID (GABA) RECEPTOR MODEL

• GABA IS THE MAJOR INHIBITORY NEUROTRANSMITTER IN THE CNS.

• MANY ANTIANXIETY DRUGS TARGET THE GABA RECEPTOR.

• BENZODIAZEPINES (BZS) ENHANCE THE INHIBITORY EFFECTS OF GABA,WHICH HAS A STRONG REGULATORY OR INHIBITORY EFFECT ON SEROTONIN (5-HT), NOREPINEPHRINE, AND DOPAMINE SYSTEMS.

• ANXIETY SYMPTOMS MAY BE LINKED TO UNDERACTIVITY OF GABA SYSTEMS OR DOWNREGULATED CENTRAL BZ RECEPTORS.

• IN PATIENTS WITH GAD, BZ BINDING IN THE LEFT TEMPORAL LOBE IS REDUCED ABNORMAL SENSITIVITY TO ANTAGONISM OF THE BZ BINDING SITE AND DECREASED BINDING WAS DEMONSTRATED IN PANIC DISORDER.

• ABNORMALITIES OF GABA INHIBITION MAY LEAD TO INCREASED RESPONSE TO STRESS IN PTSD PATIENTS.

NEUROTRANSMITTER IN CIRCUITS

AMYGDALA CENTRED CIRCUIT

[ FEAR LOOP]

• 5HT

• GABA

• GLUTAMATE

•CRF/HPA• NE• VOLTAGE GATED ION CHANNELS.

CSTC [WORRY LOOP]

• 5HT

• GABA

• GLUTAMATE

•DA• NE

• VOLTAGE GATED ION CHANNEL.

SYMPTOMS

GENERALIZED ANXIETY DISORDER

• THE DIAGNOSTIC CRITERIA FOR GAD REQUIRE PERSISTENT SYMPTOMS FOR MOST DAYS FOR AT LEAST 6 MONTHS.

• THE ESSENTIAL FEATURE OF GAD IS UNREALISTIC OR EXCESSIVE ANXIETY AND WORRY ABOUT A NUMBER OF EVENTS OR ACTIVITIES OR OTHER IMPORTANT AREAS OF FUNCTIONING.

PRESENTATION OF GENERALIZED ANXIETY DISORDER

• PSYCHOLOGICAL AND COGNITIVE SYMPTOMS :• EXCESSIVE ANXIETY• WORRIES THAT ARE DIFFICULT TO CONTROL• FEELING KEYED UP OR ON EDGE• POOR CONCENTRATION OR MIND GOING BLANK

• PHYSICAL SYMPTOMS :• RESTLESSNESS• FATIGUE• MUSCLE TENSION• SLEEP DISTURBANCE• IRRITABILITY

PANIC DISORDER

• PANIC DISORDER BEGINS AS A SERIES OF UNEXPECTED (SPONTANEOUS) PANIC ATTACKS INVOLVING AN INTENSE, TERRIFYING FEAR SIMILAR TO THAT CAUSED BY LIFE-THREATENING DANGER.

• DURING AN ATTACK, PATIENTS OFTEN DESCRIBE AN OVERWHELMING SENSE OF DOOM, A FEAR OF DYING OR LOSING CONTROL.

• PANIC ATTACKS USUALLY LAST NO MORE THAN 20 TO 30 MINUTES,

• WITH THE PEAK INTENSITY OF SYMPTOMS WITHIN THE FIRST 10 MINUTES.

• SECONDARY TO THE PANIC ATTACKS, MANY PATIENTS EVENTUALLY DEVELOP AGORAPHOBIA.

SYMPTOMS OF A PANIC ATTACK

• PSYCHOLOGICAL SYMPTOMS

• DEPERSONALIZATION• DEREALIZATION• FEAR OF LOSING CONTROL• FEAR OF GOING CRAZY• FEAR OF DYING.

• PHYSICAL SYMPTOMS :

• ABDOMINAL DISTRESS• CHEST PAIN OR DISCOMFORT• CHILLS• DIZZINESS OR LIGHT-HEADEDNESS• FEELING OF CHOKING• HOT FLUSHES• PALPITATIONS• NAUSEA• SHORTNESS OF BREATH• SWEATING• TACHYCARDIA• TREMBLING OR SHAKING.

SOCIAL ANXIETY DISORDER

• SAD IS CHARACTERIZED BY AN INTENSE, IRRATIONAL, AND PERSISTENT FEAR OF BEING NEGATIVELY EVALUATED OR SCRUTINIZED IN AT LEAST ONE SOCIAL OR PERFORMANCE SITUATION.

• EXPOSURE TO THE FEARED CIRCUMSTANCE USUALLY PROVOKES AN IMMEDIATE SITUATION-RELATED PANIC ATTACK.

• ADULTS WITH SAD USUALLY RECOGNIZE THEIR FEAR IS EXCESSIVE AND UNREASONABLE; HOWEVER, THEY ARE UNABLE TO OVERCOME IT WITHOUT TREATMENT.

WHY CAN’T I TALK TO

PEOPLE ?

SOCIAL ANXIETY DISORDER

• IN INDIVIDUALS UNDER 18 YEARS OF AGE, THE DURATION OF SYMPTOMS IS AT LEAST 6 MONTHS. THE FEAR OR AVOIDANCE IS NOT CAUSED BY A DRUG OR OTHER SUBSTANCE (E.G., COCAINE), OR A GENERAL MEDICAL OR PSYCHIATRIC DISORDER.

• THE MEAN AGE OF ONSET OF SAD IS DURING THE MID-TEENS. RATES OF SAD ARE SLIGHTLY HIGHER AMONG WOMEN THAN MEN AND MORE FREQUENT IN YOUNGER COHORTS. IT IS A CHRONIC DISORDER WITH A MEAN DURATION OF 20 YEARS.

POST TRAUMATIC

STRESS DISORDER

POSTTRAUMATIC STRESS DISORDER (PTSD)

• POSTTRAUMATIC STRESS DISORDER (PTSD) IS A CONDITION MARKED BY THE DEVELOPMENT OF SYMPTOMS AFTER EXPOSURE TO TRAUMATIC LIFE EVENTS.

• THE PERSON REACTS TO THIS EXPERIENCE WITH FEAR AND HELPLESSNESS, PERSISTENTLY RELIVES THE EVENT, AND TRIES TO AVOID BEING REMINDED OF IT.

• PTSD CAN OCCUR AT ANY AGE, AND THE COURSE IS VARIABLE.

• ONE-THIRD OF PATIENTS WITH PTSD HAVE A POOR PROGNOSIS, AND ABOUT 80% HAVE A CONCURRENT DEPRESSION OR ANXIETY DISORDER.

THE HIPPOCAMPUS AND RE-EXPERIENCING

AMYGDALA

HIPPOCAMPUS

• ANXIETY CAN BE TRIGGERED NOT ONLY BY AN EXTERNAL STIMULUS BUT ALSO BY AN INDIVIDUAL’S MEMORIES. TRAUMATIC MEMORIES STORED IN THE HIPPOCAMPUS CAN ACTIVATE THE AMYGDALA, CAUSING THE AMYGDALA, IN TURN, TO ACTIVATE OTHER BRAIN REGIONS AND GENERATE A FEAR RESPONSE.

• THIS IS TERMED RE-EXPERIENCING, AND IT IS A PARTICULAR FEATURE OF POSTTRAUMATIC STRESS DISORDER.

PTSD SYMPTOMS

RE-EXPERIENCING SYMPTOMS

AVOIDANCE SYMPTOMS

• RECURRENT, INTRUSIVE DISTRESSING MEMORIES OF THE TRAUMA

• RECURRENT, DISTURBING DREAMS OF THE EVENT• FEELING THAT THE TRAUMATIC EVENT IS RECURRING (E.G.,

DISSOCIATIVE FLASHBACKS)• PHYSIOLOGIC REACTION TO REMINDERS OF THE TRAUMA

• AVOIDANCE OF CONVERSATIONS ABOUT THE TRAUMA• AVOIDANCE OF THOUGHTS OR FEELINGS ABOUT THE

TRAUMA, AVOIDANCE OF ACTIVITIES THAT ARE REMINDERS OF THE EVENT

• AVOIDANCE OF PEOPLE OR PLACES THAT AROUSE RECOLLECTIONS OF THE TRAUMA

• INABILITY TO RECALL AN IMPORTANT ASPECT OF THE TRAUMA

• ANHEDONIA• RESTRICTED AFFECT• SENSE OF A FORESHORTENED FUTURE (E.G., DOES NOT

EXPECT TO HAVE A CAREER, MARRIAGE)

• HYPER-AROUSAL SYMPTOMS• DECREASED CONCENTRATION

• EASILY STARTLED

• HYPERVIGILANCE

• INSOMNIA

• IRRITABILITY OR ANGRY OUTBURSTS

• SUBTYPES• ACUTE: DURATION OF SYMPTOMS IS LESS THAN 3 MONTHS

• CHRONIC: SYMPTOMS LAST FOR LONGER THAN 3 MONTHS

• WITH DELAYED ONSET: ONSET OF SYMPTOMS IS AT LEAST 6 MONTHS POSTTRAUMA

OBSESSIVE-COMPULSIVE DISORDER (OCD)

OBSESSIVE-COMPULSIVE DISORDER (OCD)

• OBSESSIVE-COMPULSIVE DISORDER (OCD) IS ONE OF THE TEN LEADING CAUSES OF DISABILITY.

• PATIENTS WITH OCD EXPERIENCE SIGNIFICANT IMPAIRMENT IN THEIR QUALITY OF LIFE (QOL), WITH REDUCTIONS IN SOCIAL, FAMILY, AND OCCUPATIONAL FUNCTIONING.

• BECAUSE OF THE NATURE AND POTENTIAL SEVERITY OF SIGNS AND SYMPTOMS AND THE RESULTANT NEGATIVE EFFECTS ON QOL, OCD IS CONSIDERED A MAJOR MEDICAL CONDITION.

NEURAL CIRCUITS OF OBSESSION/WORRY

THALAMUS

STRIATUM

DLPFC SHOWN HERE IS A CORTICO-STRIATOTHALAMO- CORTICAL (CSTC) LOOP ORIGINATING AND ENDING IN THE DORSOLATERAL PREFRONTAL CORTEX (DLPFC).

OVERACTIVATION OF THIS CIRCUIT MAY LEAD TO WORRY OR OBSESSIONS.

PRESENTATION

• OBSESSIONS• REPETITIVE THOUGHTS (E.G., FEELING CONTAMINATED AFTER TOUCHING AN OBJECT,

DOUBTING WHETHER THE STOVE WAS TURNED OFF)

• REPETITIVE IMAGES (E.G., RECURRENT SEXUALLY EXPLICIT PICTURES)

• REPETITIVE IMPULSES (E.G., NEED FOR SYMMETRY OR PUTTING THINGS IN SPECIFIC ORDER, IMPULSE TO SHOUT OUT OBSCENITIES IN A TEMPLE)

• COMPULSIONS• REPETITIVE ACTIVITIES (E.G., HAND WASHING, CHECKING, ORDERING, NEED TO ASK,

NEED TO CONFESS)

• REPETITIVE MENTAL ACTS (E.G., COUNTING, REPEATING WORDS SILENTLY, PRAYING)

DRUGS ASSOCIATED WITH ANXIETY SYMPTOMS

• ANTICONVULSANTS: CARBAMAZEPINE

• ANTIDEPRESSANTS: SELECTIVE SEROTONIN REUPTAKE INHIBITORS, TRICYCLIC ANTIDEPRESSANTS

• ANTIHYPERTENSIVES: FELODIPINE• ANTIBIOTICS: QUINOLONES,

ISONIAZID• BRONCHODILATORS: ALBUTEROL,

THEOPHYLLINE• CORTICOSTEROIDS: PREDNISONE• DOPA AGONISTS: LEVODOPA

• HERBALS: MA HUANG, GINSENG, EPHEDRA

• NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: IBUPROFEN

• STIMULANTS: AMPHETAMINES, METHYLPHENIDATE, CAFFEINE, COCAINE

• SYMPATHOMIMETICS: PSEUDOEPHEDRINE

• THYROID HORMONES: LEVOTHYROXINE• TOXICITY: ANTICHOLINERGICS,

ANTIHISTAMINES, DIGOXIN• WITHDRAWAL: ALCOHOL, SEDATIVES.

MEDICAL DISEASES ASSOCIATED WITH ANXIETYCOMMON MEDICAL ILLNESSES ASSOCIATED WITH ANXIETY SYMPTOMS

CARDIOVASCULAR :

• ANGINA, ARRHYTHMIAS, CONGESTIVE HEART FAILURE, ISCHEMIC HEART DISEASE, MYOCARDIAL INFARCTION

ENDOCRINE AND METABOLIC :

• CUSHING’S DISEASE, HYPERPARATHYROIDISM, HYPERTHYROIDISM, HYPOTHYROIDISM, HYPOGLYCEMIA, HYPONATREMIA, HYPERKALEMIA, PHEOCHROMOCYTOMA, VITAMIN B12 OR FOLATE DEFICIENCIES

NEUROLOGIC :

• DEMENTIA, MIGRAINE, PARKINSON’S DISEASE, SEIZURES, STROKE, NEOPLASMS, POOR PAIN CONTROL

RESPIRATORY SYSTEM :

• ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, PULMONARY EMBOLUS, PNEUMONIA

OTHERS :

• ANEMIAS, SYSTEMIC LUPUS ERYTHEMATOSUS, VESTIBULAR DYSFUNCTION

MANAGEMENT

INVESTIGATIONS

• BLOOD SUGAR – T2 DM

• LIPID PROFILE

• CORTISOL LEVEL

• URINE DRUG SCREEN: SHOULD BE ORDERED TO RULE OUT SUSPECTED STIMULANT ABUSE

• TFTS: RECOMMENDED IF THE PATIENT HAS SUSPECTED THYROID DISEASE (E.G., WEIGHT LOSS, GOITRE)

• 24-HOUR URINE TEST FOR VANILLYLMANDELIC ACID AND METANEPHRINES: ORDERED TO RULE OUT PHAEOCHROMOCYTOMA IF CARDIAC SYMPTOMS SUCH AS TACHYCARDIA AND/OR HYPERTENSION ARE PRESENT

• ECG AND ECHOCARDIOGRAM: RECOMMENDED FOR PATIENTS WITH A HIGH RISK OF CARDIAC DISEASE OR EVIDENCE OF CARDIAC DISEASE

• PULMONARY FUNCTION TESTS: SHOULD BE CONSIDERED FOR PATIENTS WITH SHORTNESS OF BREATH AND EVIDENCE OF PULMONARY DISEASE

• EEG: USEFUL FOR EVALUATING PATIENTS WHERE ANXIETY IS SUSPECTED TO BE A SEIZURE PRODROMAL SYMPTOM.

SCALES

COMMONLY USED

• HAMILTON’S ANXIETY RATING SCALE

• BECK ANXIETY INVENTORY (BAI)

TREATMENT

PHARMACOLOGICALNON-PHARMACOLOGICAL/

PSYCHOTHERAPY

PHARMACOLOGICAL

PHARMACOLOGICAL

• 3 MAJOR NEUROTRANSMITTERS ARE TARGETTED IN PHARMACOLOGICAL TREATMENT OF ANXIETY DISORDERS

1. GABA - A. BENZODIAZEPINES

2. SEROTONIN - B. SSRIs

3. NOREPINEPHRIN - C. SNRIs

A) BENZODIAZEPINES

• BENZODIAZEPINES, PERHAPS THE BEST-KNOWN AND MOST WIDELY USED ANXIOLYTICS, ACT BY ENHANCING GABA ACTIONS AT THE LEVEL OF THE AMYGDALA AND AT THE LEVEL OF THE PREFRONTAL CORTEX WITHIN CSTC LOOPS TO RELIEVE ANXIETY.

3 MAJOR TYPES

1,4 BENZODIAZEPINES

1,5 BENZODIAZEPINES

2,3 BENZODIAZEPINES

1,4 BENZODIAZEPINES

• ADVANTAGES:• ANXIOLYSIS

• SEDATION,

• MUSCLE RELAXATION

• DISADVANTAGES• COGNITIVE AND PSYCHOMOTOR IMPAIRMENT

• ADDICTIVENESS

• EG – LORAZEPAM, CLONAZEPAM, OXAZEPAM, FLUNITRAZEPAM, CHLORDIAZEPOXIDE, DIAZEPAM ETC

1,5 BENZODIAZEPINE

• CLOBAZAM

• ADVANTAGES & DISADVANTAGES• ANXIOLYTIC

• ANTIEPILEPTIC

• DECREASED SEDATION

• LOW DEPENDENCE

• LOW MUSCLE RELAXATION

• CAN BE USED IN EXECUTIVE GROUPS

• CAN BE CONTINUED FOR LONG PERIOD OF TIME

2,3 BENZODIAZEPINES

• TOFISOPAM• TOFISOPAM, A RACEMIC 2,3-BENZODIAZEPINE

COMPRISED OF R- AND S-ENANTIOMERS, IS UNLIKE TRADITIONAL 1,4-BENZODIAZEPINES.

• ADVANTAGES

• LIKE OTHER BENZODIAZEPINES, IT POSSESSES ANXIOLYTIC PROPERTIES BUT UNLIKE OTHER BENZODIAZEPINES IT DOES NOT HAVE ANTICONVULSANT*, SEDATIVE, SKELETAL MUSCLE RELAXANT, MOTOR SKILL-IMPAIRING OR AMNESTIC PROPERTIES.

*WHILE IT MAY NOT BE AN ANTICONVULSANT IN AND OF ITSELF, IT HAS BEEN SHOWN TO ENHANCE THE ANTICONVULSANT ACTION OF CLASSICAL 1,4-BENZODIAZEPINES SUCH AS

DIAZEPAM.

BETTER RESOLUTION OF ANXIETY & EXISTING DEPRESSION WITHOUT SEDATION, MUSCLE

RELAXATION

CLIN.TRIAL SUGGEST IT TO BE USEFUL IN ANXIETY DISORDERS, ANXIETY NEUROSIS, MIXED ANXIETY

DEPRESSION, SOMATOFORM DISORDER, ALCOHOL WITHDRAWAL, MENOPAUSAL SYNDROME

BINDS TO 2,3 BDZS SITES IN THE

SUBCORTICAL AREA.

IT DOES NOT BIND TO GABA-A RECEPTOR

COMPLEX IN CORTICAL AREAS

B) SELECTIVE SEROTONIN REUPTAKE INHINITOR

• SEROTONIN IS A KEY NEUROTRANSMITTER THAT INNERVATES THE AMYGDALA AS WELL AS ALL THE ELEMENTS OF CSTC CIRCUITS, NAMELY, PREFRONTAL CORTEX, STRIATUM, AND THALAMUS, AND THUS IS POISED TO REGULATE BOTH FEAR AND WORRY.

• ANTIDEPRESSANTS THAT CAN INCREASE SEROTONIN OUTPUT BY BLOCKING THE SEROTONIN TRANSPORTER (SERT) ARE ALSO EFFECTIVE IN REDUCING SYMPTOMS OF ANXIETY AND FEAR IN EVERY ONE OF THE ANXIETY DISORDERS

SOME WIDELY USED SSRIs

• FLUOXETINE

• PAROXETINE

• ESCITALOPRAM

• SERTRALINE

• FLUVOXAMINE

• SIDE EFFECTS: STOMACHACHE, INCREASED ACTIVITY LEVEL, INSOMNIA, AGITATION/DISINHIBITION AT HIGHER DOSES

• LESS OFTEN DIARRHEA, HEADACHES, TICS, CRAMPS/TWITCHING, SEXUAL SIDE EFFECTS.

• START AT A LOW DOSE AND INCREASE SLOWLY BASED ON TREATMENT RESPONSE AND SIDE EFFECTS

C) NOREPINEPHRINE REUPTAKE INHIBITOR

SYMPTOMS OF HYPERAROUSAL SUCH AS NIGHTMARES CAN BE REDUCED AND WORRY CAN BE REDUCED BY NOREPINEPHRINE REUPTAKE INHIBITORS (ALSO CALLED NET OR NOREPINEPHRINE TRANSPORTER INHIBITORS).

HYPERACTIVITY OF CSTC

NRI ACTION ON NE NEURONALOUTPUT TO CSTC

SOME NRIs & SNRIs COMMONLY USED

• SEROTONIN–NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS)

• VENLAFAXINE

• DESVENLAFAXINE

• DULOXETINE

• MILNACIPRAN

• LEVOMILNACIPRAN

• NOREPINEPHRINE REUPTAKE INHIBITORS (NRIS)

• ATOMOXETINE

• REBOXETINE

• VILOXAZINE

OTHER COMMONLY USED DRUGS

• GABAPENTIN AND PREGABALIN

• ALSO KNOWN AS α2δ LIGANDS

• BIND TO THE α2δ SUBUNIT OF PRESYNAPTIC N AND P/Q VSCCS, BLOCK THE RELEASE OF EXCITATORY NEUROTRANSMITTERS SUCH AS GLUTAMATE WHEN NEUROTRANSMISSION IS EXCESSIVE.

• THEY HAVE DEMONSTRATED ANXIOLYTIC ACTIONS IN SOCIAL ANXIETY DISORDER AND PANIC DISORDER

• 5-HT1A RECEPTOR PARTIAL AGONIST - BUSPIRONE

OTHER COMMONLY USED DRUGS

• MONOAMINE OXIDASE INHIBHITORS

• HYDROXYZINE

• ANTI-PSYCHOTICS – HAS LIMITED EVIDENCE AND HIGH SIDE EFFECTS

• PROPRANOLOL & OXPRENOLOL- LICENSED TO TREAT ANXIETY SYMPTOMS- USED IN PTSD

PSYCHOTHERAPY IN ANXIETY DISORDER

NUMEROUS STUDIES HAVE SHOWN THE IMPORTANCE OF COMBINING PSYCHOTHERAPY WITH PHARMACOTHERAPY IN ANXIETY DISORDERS.

Psychotherapy was significantly more efficacious than pharmacotherapy in obsessive-compulsive disorder (g=0.64). Furthermore, pharmacotherapy was significantly more efficacious than non-directive counseling (g=0.33), and psychotherapy was significantly more efficacious than pharmacotherapy with tricyclic antidepressants (g=0.21).

There was sufficient evidence that combined treatment is superior for major depression, panic disorder, and obsessive compulsive disorder (OCD). The effects of combined treatment compared with placebo only were about twice as large as those of pharmacotherapy compared with placebo only, underscoring the clinical advantage of combined treatment. The results also suggest that the effects of pharmacotherapy and those of psychotherapy are largely independent from each other, with both contributing about equally to the effects of combined treatment.

TYPES OF PSYCHOTHERAPY

1. BEHAVIOUR THERAPY

2. COGNITIVE BEHAVIOUR THERAPY

3. PSYCHOANALYTIC PSYCHOTHERAPY

BEHAVIOUR THERAPY

• EXPOSURE AND RESPONSE PREVENTION• SYSTEMATIC DESENSITIZATION• IMPLOSIVE THERAPY/FLOODING

• ANXIETY MANAGEMENT • RELAXATION TECHNIQUES – YOGA, ZEN, JPMR• BIOFEEDBACK

• DESENSITIZATION OF THE STIMULUS

• EYE MOVEMENT DESENSITIZATION AND REPROCESSING

• SOCIAL SKILLS TRAINING

COGNITIVE BEHAVIOUR THERAPY

• CONTROL OF AUTOMATIC THOUGHTS

• CORRECTION OF COGNITIVE ERRORS

• BREAKING THE ASSOCIATION BETWEEN THE EVENTS, COGNITIVE AROUSAL AND MALADAPTIVE BEHAVIOUR

PSYCHOANALYTIC PSYCHOTHERAPY

• THE PSYCHOANALYTIC PROCESS INVOLVES BRINGING TO THE SURFACE REPRESSED MEMORIES AND FEELINGS BY MEANS OF A SCRUPULOUS UNRAVELING OF HIDDEN MEANINGS OF VERBALIZED MATERIAL AND OF THE UNWITTING WAYS IN WHICH THE PATIENT WARDS OFF UNDERLYING CONFLICTS THROUGH DEFENSIVE FORGETTING AND REPETITION OF THE PAST.

PSYCHOANALYTICALLY ANXIETY IS CLASSIFIED INTO 4 TYPESTHE CLASSIFICATION IS BASED ON THE TYPES OF PRIMARY COMPLEX AND THE SUBSEQUENT NATURE OF ITS CONFLICT WITH THE EGO (CONSCIOUS MIND).

1. TRAUMATIC ANXIETY (PANIC ATTACK) – EGO BECOMES PARALYSED

2. SEPARATION ANXIETY – SEPARATION FROM LOVED/VALUABLE OBJECTS

3. CASTRATION ANXIETY – LOSS OF LOVED/VALUABLE OBJECT

4. SUPEREGO ANXIETY

DEPENDING ON THE TYPE OF ANXIETY PSYCHOANALYTIC METHODS ARE ADAPTED.

UNCONSCIOUS

CONSCIOUS

PRECONSCIOUS

EGO

CONFLICTS TRYING TO ACCESS THE CONSCIOUS MIND

THROUGH PRECONSCIOUS

A STRONG EGO SUPRESSES THEM

UNCONSCIOUS

CONSCIOUS

PRECONSCIOUS

EGO

WHEN EGO IS WEAK IT FAILS TO SUPRESS

X THE CONFLICTS GAINS ACCESS TO THE CONSCIOUS MIND

ANXIETY SYMPTOMS

ANXIETY DISORDER PHARMACY

GAD

1ST LINE

2ND LINE

3RD LINE

SOCIALANXIETY

DISORDER

1ST LINE

2ND LINE

3RD LINE

PANIC DISORDER

1ST LINE

2ND LINE

3RD LINE

PTSD

1ST LINE

2ND LINE

3RD LINE

RECENT ADVANCES IN TREATMENT OF ANXIETY DISORDERS

• NMDA AGONIST

• D-CYCLOSERINE

• MEMANTINE

THANK YOU