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Psychopharmachology

Lecture 4 – Anxiety Disorders and Treatment

Depression Overview

Neurotransmitters in Depression

Norepinephrin – Effects behavioral activation, arousal and mental filter aspect of attention. Absence leads to lethargy poor attentional control.

Dopamine – Pleasure, desire and motivation. Low levels of dopamine lead to anhedonic symptoms.

Seratonin – Satiation, here and now happiness, and absence is guilt and worry.

Biological Treatments of Depression

Trycyclics: Second generation anti-depressent medications. These medications effect serotonin and norepinephrine. They have limited to no effect on dopamine.

SSRI: Are focused at the reuptake process and specifically serotonin. They treat anxiety and are used as adjunt treatment in multiple health and mental health dissorders (1–4 weeks while the body adapts to the drug and 6 to 8 weeks to full effect).

SNRI: Are focused on the reuptake of serotonin and norepiniphrine. They can be activating.

Welbutrin: Works on dopamine and norepinephrine. Is activating, is used to treat smoking and or weight loss. A common of lable use is the treatment of ADHD.

Anxiety Disorders Overview

300.02 Generalized anxiety disorder

300.21 Panic with agoraphobia 300.01 Without agoraphobia 300.22 Agoraphobia without history of panic disorder

300.29 Specific phobia

300.23 Social phobia

300.3 Obsessive-compulsive disorder

309.81 Posttraumatic stress disorder

308.3 Acute stress disorder

293.84 Anxiety disorder due to a general medical condition

293.89 Anxiety disorder due to... [indicate the general medical condition]

300.00 Anxiety disorder NOS

Paul D. MacLean 1913-2007 coined the concept of the limbic system in 1952 and went on to place the limbic system into an evolutionary context. He proposed that the human brain is really

three brains in one, a "triune brain."

Triune Brain

Autonomic Nervious System

Autonomic Nervous SystemStress Response

Poly-Vagal TheoryThe way it works…

V.V.C. Brake Disengages

Sympathetic Nervous system Engages

V.V.C Brake Engaged at rest and Socially Engaged.

DMNX EngagesShutting Down Consciousness

Stress Reactions

Stress Response in The Brain

Fig. 2. The bed nucleus of the stria terminalis and central nucleus of the amygdala receive projections from the basolateral amygdala and project, in turn, to downstream target areas that mediate many of the behavioral, autonomic, and electrophysiological consequences of fear and anxiety, some of which are shown here.

Fear: Short-term and conditioned through classical conditioning principals.

8 mil seconds from trigger to startle response

Anxiety: Long-term and activated in the background. Does not follow conditioned stimulus. Triggerd CRH (e.g. dark ally) make startle more likely.

Quantitative volumetric MRI revealed a bilateral reduction in temporal lobe volume in patients with PD compared to HC subjects. The AHC (Amygdala Hippocampal Complex) was normal. The right frontal lobe volume was also decreased. Using VBM we detected a significant GM volume reduction in the right middle temporal gyrus [Brodmann area (BA) 21] in patients with PD. In addition, there was a reduction in GM volume in the medial part of the orbitofrontal cortex

Reff: PMID: 20056020 NOTE: Image not from the quated study and ment to be a discription of brain behavior not a research data point.

Talking to Your Client About Medications

You do not need to pretend to have information you do not have.

Good lines are, “lets look it up together” or “I will consult and get back to you.”

Be ready to help some one deal with the feeling of shame and worry about stigma while building a mental health positive identity.

Talking to Your Client About Medications

Assessment: Assess beliefs, fears and worries about medications. Assess side effects duration, intensity and frequency.

Look up side effects, consult with a provider and develop plan to minimize their impact.

Address Concerns: Normalize and use as opportunity to develop increased self

acceptance. Support client to discuss concerns with clinician. (Clinical

goal: Healthy boundaries and assertiveness). Support cleint to research normal and high risk side effects

and empower them to understand their treatment.

Anxiety Psychopharm Quick Refference

SSRIs: Change serotinin and are the first line of treatment for anxiety.

SNRI’s and Welbutrin: Change norepinephrine (SNRI’s), Change predominantly dopamine (Buproprion).

Buspar: A good treatment for GAD. Buspirone functions as a serotonin 5-HT1Areceptor partial agonist. It is this action that is thought to mediate its anxiolytic and antidepressant effects.

Antipsychotics: Studies as main treatment show effective tx for GAD and social anxiety questions about respiridal as a main treatment. Often used as adjunct tx for anxiety. Has poor adherence due to side effects.

Anxiety Psychopharm Quick Refference

Benzodiazipines: Effect GABA. GABA Is a neurotransmitter associated with overall reduced activation in the brain. It has a sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant

Betablockers: Beta-blockers control some of the physical symptoms of anxiety, such as trembling and sweating.

Trycylics antidepressants can be effective for anxiety. They tend to be sedating.

SSRIs and SNRIs Anxiety Treatment

SNRI - Venlafaxine (Effexor) is commonly used to treat GAD

SSRIs - fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro), paroxetine (Paxil), and citalopram (Celexa) are prescribed for multiple anxiety disorders: Panic disorder Obsessive Compulsive Disroder (OCD) Post-traumatic Stress Disorder (PTSD) Social phobia

Recommendations for Medication Had Little

Impact In the late 1990’s recommendations were put out to treat anxiety disorders

these recommendations inclued reduced use of Benzodiazipine meications a rocomendation of SSRI’s as firt line medication with SNRIs used in some cases.

Despite the recommendations psychotropic treatment patterns have not changed. (e.g. Benzodiazipine’s are still use first line treatments in many cases for GAD and social phobia). During the 12 years of this study the use of SSRIs and SNRI’s as stand alone medications is low.

“Treatment recommendations for use of SSRIs and venlafaxine in the management of generalized anxiety disorder and social phobia initially promulgated in 1998 had a modest impact on changes in psychopharmacologic practice 4–5 years later.”

Change in medical practice is difficult and takes time. Our work with clinicians can have a powerful impact.

DOI: 10.1002/da.20089

Tricyclic Medications

Tricyclic antidepressants can be effective for anxiety. They tend to be sedating.

Imipramine (Tofranil) is prescribed for panic disorder and GAD.

Clomipramine (Anafranil) is used to treat OCD.

RULE OF THUMB: Start low and go slow.

Trcyclic medications can be used to impact sleep – Trazadone (25 mg to 50 mg) is aimed at effecting sleep.

Beta-Blockers – Reduce body signals of anxiety

Beta-blockers control some of the physical symptoms of anxiety, such as trembling and sweating.

Propranolol (Inderal) is a beta-blocker usually used to treat heart conditions.

e.g. when a person with social phobia must face giving a speech a doctor may prescribe a beta-blocker.

Side Effects of Betablockers

Fatigue

Cold hands

Dizziness – Taking a pre-event dose can help the individual know how they will react to medication.

Weakness

NOTE: Beta-blockers generally are not recommended for people with asthma or diabetes because they may worsen symptoms.

Benzodiazipines

Benzodiazepines – Mechaism Gabanergic enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA-A).

GABA – Is a neurotransmitter associated with overall reduced activation in the brain. It has a sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant Clonazepam (Klonopin), which is used for social phobia and GAD Lorazepam (Ativan), which is used for panic disorder Alprazolam (Xanax), which is used for panic disorder and GAD.

Fast acting (with in minuets or hours of administration).Can be addictive and the medication can become a obstical to effective treatment.

Disinhabition – Pill Based Courage – Leads to increased impulsivity and aggression at times.

Benzodiazipines Continued

Chlordiazepoxide is the most commonly used benzodiazepine for alcohol detoxification.

The mechanism of action for bothalcohol and benzodiazipines is similar and thus the medications can control symptoms DTs.

Benzodiazipines Continued

Short-acting compounds have a median half-life of 1–12 hours. They have few residual effects if taken before bedtime, rebound insomnia

may occur upon discontinuation, and rebound anxiety with prolonged usage. Examples are brotizolam, midazolam, and triazolam.

Intermediate-acting compounds have a median half-life of 12–40 hours. They may have some residual effects in the first half of the day if used as a

hypnotic. Rebound insomnia more common for intermediate the long-acting Examples are alprazolam, estazolam, flunitrazepam, clonazepam,

lormetazepam, lorazepam, nitrazepam, and temazepam.

Long-acting compounds have a half-life of 40–250 hours. For those with slow metabolism and elimination they have risk of

accumulation. but they have a reduced severity of rebound effects and withdrawal.

Examples are diazepam, clorazepate, chlordiazepoxide, and flurazepam.

Buspar – Anxiolytic

Treatment for GAD – Generalized Anxiety Dissorder.

Buspirone functions as a serotonin 5-HT1Areceptor partial agonist. It is this action that is thought to mediate its anxiolytic and antidepressant effects.

Additionally, it functions as a presynaptic dopamine antagonist D2, as well as a partial α1 receptor agonist.

CONTRAINDICATIONS: Metabolic acidosis as in diabetes.

Interactions with: Haldol (increases haldol levels) Nefazodone (increased buspar levels), Tegratol (decrease buspar levels), grapefruit juice (deacreses significantly buspar levels).

Buspar

Anxiety Treatmen

t and Client

Ratings.

Atypical Antipsychotic Medications and Anxiety

The review of randomized control trials (4144 participants) on three second-generation antipsychotics (olanzapine, quetiapine, risperidone). Nine studies investigated the effects of second-generation antipsychotics

in generalised anxiety disorder. Two studies investigated the effects in social phobia.

There were no studies on panic disorder or any other primary anxiety disorder.

Seven studies on Quetiapine found efficacy compared to placebo for GAD. When compared with antidepressants equivilant efficacy-related outcomes. Higher dropout in Quetiapine due to adverse events, gained weight and feeling sedated.

Olanzapine and found no difference in response to treatment.

Two trials compared adjunctive treatment with risperidone with placebo and found no difference in response to treatment.DOI: 10.1002/14651858.CD008120.pub2

A Comparison Trial: GAD Treatment Critical Thinking

Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs.

During the first 2 weeks of treatment, 2′-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. (Slow Acting Benzodiazipine)

Both paroxetine and imipramine treatment resulted in more improvement than 2’-chlordesmethyldiazepam by the fourth week of treatment.

Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2′-chlordesmethyldiazepam affects predominantly somatic symptoms.

DOI: 10.1111/j.1600-0447.1997.tb09660.x

Role Play

Cost of Comorbid Anxiety and Health Conditions

The average total annual cost for all the GAD patients in the study was $7451.

Compared with patients with GAD-only, the estimated total cost was $762 higher for GAD with depression (p < 0.001).

$2989 higher for GAD with pain (p < 0.001).

$6073 higher for GAD with both depression and pain (p < 0.001).

doi: 10.1097/NMD.0b013e3181963486.

Copyright © American Psychiatric Association. All rights reserved.

From: Anxiety Disorders and Comorbid Medical Illness Focus. 2008;6(4):467-

485.

Rome III Guidelines for the Medical and Psychological Treatment of IBS.

Figure Legend:

Date of download: 10/21/2012

Copyright © American Psychiatric Association. All rights reserved.

From: Anxiety Disorders and Comorbid Medical Illness

Focus. 2008;6(4):467-485.

Number of 30-Day Role Impairment Days Associated With Comorbid DSM-III-R Mental Disorders Among NCS-R Respondents With Chronic Physical Disorders

Figure Legend:

Anxiety and Irritable Bowl Syndrome

Co-morbid IBS and anxiety corealtes with increased severity of GI symptoms and more dissability.

CBT has several studies but limited double blind studies but is considered effective.

Tricyclic antidepressants (TCAs) more effective than SSRI (central analgesic actions of norep.)

SSRIs are effective for underlying anxiety and depression, and possibly for IBS sufferers without psychiatric disorders.

The benzodiazepines have some studies showing efficacy for reducing anxiety and limited for effecting the IBS sympt. but due to tolerance and addiction not recommended.

Buspar: May be effective but no clear data exists to date.

Activation of CRF1 signaling pathways and IBS-like manifestations, which can be blocked by CRF1 receptor antagonists.

COPD and Anxiety

“COPD is associated with a higher risk of anxiety. Once anxiety develops among patients with COPD, it is related to poorer health outcomes.”

Participants with COPD (n=1202) and matched controls without COPD (n=302). doi:10.1136/thx.2009.126201

Both CBT group treatment and COPD education can achieve sustainable improvements in QoL for COPD patients experiencing moderate-to-severe symptoms of depression or anxiety.

Asthma and Anxiety

“Panic disorder, panic attacks, GAD and phobias appear to be the anxiety disorders most strongly associated with asthma.”

“In youth: a significant correlation between anxiety sensitivity and asthma severity.”

“One study found that adolescents with a history of life-threatening asthma attacks are more likely to have symptoms of PTSD due to asthma attacks.”

“Comorbid anxiety and depressive disorders are only accurately diagnosed in approximately 40% of asthmatic patients in primary care.”

doi:10.1080/02770900701840238

Asthma and Anxiety

Psychological Treatments: (data on efficacy inconclusive at this time)

“Relaxation therapy reduced the need for rescue bronchodilators.”

“CBT improved quality of life in two other studies.”

“Spirometry measures improved following bio-feedback in two studies, but not with relaxation therapy in four studies.”

doi:10.1080/02770900701840238

Case Discussion

Closing Questions

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