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Treatment Resistant Depression

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Sophia F. Dziegielewski, Ph.D., LCSW

Upon completion of this seminar the professional will be expected to demonstrate knowledge and:

Identify important terms, myths and practices related to the

treatment of depression

Identify several methods for addressing treatment resistant

depression

Summarize the risks and benefits of using several commonly prescribed treatments for depression

Identify ways to better empower clients taking prescribed

medications for depression

Dziegielewski, S.F. Dziegielewski, S.F. Dziegielewski, S.F. Dziegielewski, S.F. (2010). Social work practice and psychopharmacology: A person and environment approach. New York: Springer Publishing.

Dziegielewski, S.FDziegielewski, S.FDziegielewski, S.FDziegielewski, S.F. (2010). DSM-IV-TR™ in action (2ndEdition). New York: Wiley Publishers. First edition published in 2001).

Dziegielewski, S.F. Dziegielewski, S.F. Dziegielewski, S.F. Dziegielewski, S.F. (2006). Psychopharmacology handbook: For the non-medically trained. New York: Norton Publishers.

Dziegielewski, S.F. Dziegielewski, S.F. Dziegielewski, S.F. Dziegielewski, S.F. (2005). Substance Addictions: Assessment and intervention. Chicago, IL: Lyceum Publications.

Speaker Contact Information: Speaker Contact Information: Speaker Contact Information: Speaker Contact Information: Sophia F. Dziegielewski, Ph.D., Sophia F. Dziegielewski, Ph.D., Sophia F. Dziegielewski, Ph.D., Sophia F. Dziegielewski, Ph.D., LCSWLCSWLCSWLCSW [email protected]

[email protected]@uc.edu

[email protected] or or or or [email protected]@[email protected]@aol.com

Lexapro Zoloft

Prednisone (reduces swelling and allergic reaction) Hydrocodone

Cymbalta (Duloxetine) depression Xanax

Wellbutrin Effexor

Vicodin (narcotic hydrocodone and non-narcotic acetaminophen) Lipitor (statin, lowers blood cholesterol, 12.9 billion in sales,

largest selling drug in the world).

6 out of 10 are mental health and two others are pain related 6 out of 10 are mental health and two others are pain related6 out of 10 are mental health and two others are pain related 6 out of 10 are mental health and two others are pain related

Exercise Sleep Diet

Medications are never enough

Relapse is now referred to as Reinstatement Compliance vs. Adherence and Constance Withdrawal is often referred to as Discontinuance

Syndrome

Compliance: Use of blister packs to make sure

medications are taken as prescribed in drug trials

Drop-Out Rates: Always using behavioral

(2)

Research and Process Groups

Bipolar Disorders Schizophrenia

Healthcare professionals and patients are

encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report Online:

www.fda.gov/MedWatch/report.htm

Download form or call 1-800-332-1088 to

request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

What are the implications of this?

Many medications have stomach problems,

N& V

At least 30% of all individuals never refill a

prescription because of concerns related to side-effects.

Three most common side effects:

Fatigue Nausea Insomnia

The liver is the main organ for metabolizing,

activating and/or deactivating drugs prior to excretion via the bile or the urine.

Sometimes drug use can cause chemical

injury to the cells.

Damage can vary from elevation of liver

enzymes to liver failure and transplantation or death.

Jaundice

Nausea and vomiting Abdominal pain Bleeding

Mental confusion Kidney failure

(3)

Atomoxetine (marketed as Strattera)

From January 2005-2008, six reported post-market cases of serious liver injury and one death.

Watch for jaundice or laboratory evidence of hepatotoxicity- discontinue at once.

Neurochemical activity

Dopamine Serotonin Norepinephrine Glutamate

GABA (Gamma-aminobutyric acid) Glycine

Step 1: Synthesis Step 2: Storage Step 3: Release

Step 4: Receptor Binding

Step 5: Termination (reuptake, enzymatic degradation and diffusion)

(4)

Can create transmitter synthesis (increase or

decrease)

Can create transmitter storage

Can promote or inhibit transmitter release Can influence receptor binding

◦Agonist versus Antagonist

Can influence termination such as blocking

reuptake

Mood Episodes

Manic, hypomanic, major depressive episode and mixed

Mood Disorders:

Bipolar I, Bipolar II, Cyclothymia Major Depressive Disorder, Dysthymia

supplement depression related medications

with a synthetic version of the hormone Cytomel (Liothronine)

Can use stimulants such as Ritalin for

treatment resistant depression

Can use beta blockers such as Visken

(Pindolol) for HBP to speed up the effects of the antidepressants

2004, the FDA ordered the strongest safety warning possible:

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and

adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone

considering the use of [Drug Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Warning was extended in 2006 to include young

adults (aged 18-24)

Be especially observant within the first few

months of antidepressant treatment or whenever there is a change in dose.

Antidepressants may increase suicidal

thoughts or behaviors in some children, adolescents, and young adults.

(5)

Effexor® (venlafaxine), Cymbalta® (duloxetine), Lexapro® (escitalopram), Celexa® (citalopram),

Zoloft® (sertraline), Paxil® (paroxetine), Prozac® (fluoxetine),

Wellbutrin® (bupropion), Zyban® (bupropion), TCAs (tricyclic antidepressants), most likely

including newer one Symbyak

MAOIs (monoamine oxidase inhibitors) Nardil®

(phenelzine)

Atypical antidepressants Sinequan® (doxepin)

Anafranil (clomipramine), Asendin (amoxapine), Aventyl (nortriptyline), Celexa (citalopram hydrobromide), Cymbalta (duloxetine, Desyrel (trazodone HCl), Effexor (venlafaxine HCl), Elavil (amitriptyline),

Etrafon (perphenazine/amitriptyline), fluvoxamine maleate, Lexapro (escitalopram hydrobromide),

Limbitrol (chlordiazepoxide/amitriptyline), Ludiomil (maprotiline), Marplan (isocarboxazid), Nardil (phenelzine sulfate),

Norpramin (desipramine HCl), Pamelor (nortriptyline) Parnate (tranylcypromine sulfate), Paxil (paroxetine HCl), Pexeva (paroxetine mesylate), Prozac (fluoxetine HCl) Remeron (mirtazapine), Sarafem (fluoxetine HCl),

Serzone (nefazodone HCl), Sinequan (doxepin), Surmontil (trimipramine), Symbyax (olanzapine/fluoxetine), Tofranil (imipramine),

Tofranil-PM (imipramine pamoate),Triavil (perphenazine/amitriptyline), Vivactil (protriptyline), Wellbutrin (bupropion HCl), Zyban (bupropion HCl) Zoloft (sertraline HCl), Prestiq (Desvenlafaxine)

Complete a comprehensive safety plan with Complete a comprehensive safety plan with Complete a comprehensive safety plan with Complete a comprehensive safety plan with

clear documentation. clear documentation. clear documentation. clear documentation.

No HarmNo HarmNo HarmNo Harm----No Risk Agreements as Standard of No Risk Agreements as Standard of No Risk Agreements as Standard of No Risk Agreements as Standard of

Practice Practice Practice Practice

I will not harm myself or someone else, if I

feel as though I could harm myself or someone else I will immediately go to the nearest emergency room at _________.

Have family member acknowledge and

document acknowledgement.

If children at risk call CPS.

REM sleep – We all need it! Assess for sleep problems

Can help with sleep- Chamomile tea,

Melatonin, Valerian, Kava

100-400 milligrams of magnesium ?

Keep noise and light to a minimum Start and keep a routine

Avoid large meals prior to sleep

Don’t drink caffeine 4-6 hrs before bedtime Stop working on tasks an hour before

bedtime to clear mind

Practice relaxation before bedtime If in pain, try Tylenol

(6)

Self-report

Self-report measures

Blood Levels

Anything designed to be strong enough to change a feeling, thought or emotion can indeed change feelings thoughts or emotions.

For antidepressants taking a medication for

at least 12 months is recommended for best results.

Quitting too soon individuals are more likely

for depression to return.

Treatment Resistant Depression (TRD)

Five Treatments Cutting Edge (2008)

3 devices 1 medicine 1 medicinal food

ECT –most rapid onset of action, high relapse

rates and cognitive side effects

Vagus Nerve Stimulation (VNS)

Transcranial Magnetic Nerve Stimulation

(TMS)

A type of treatment in which short bursts of

electrical energy are directed into the brain via the vagus nerve, a large nerve in the neck.

The energy comes from a battery, about the size of

a silver dollar, which is surgically implanted under the skin, usually on the chest.

Leads are threaded under the skin and attached to

the vagus nerve in the same procedure.

The physician programs the device to deliver small

(7)

Considered non-invasive and painless. TMS involves placing an electromagnetic

coil against the patient's scalp.

An electric current passes through this coil

that creates a magnetic pulse, which causes small electrical currents in the brain.

These currents stimulate nerve cells in the

region of the brain involved in mood regulation and depression.

The Atypical Antipsychotic

Aripiprazole (generic) ABILIFY

Approved based on positive results of two six week placebo controlled studies.

L-methyfolate

LL-LL--Methylfolate/B12/B6/B2 is a vitamin -Methylfolate/B12/B6/B2 is a vitamin Methylfolate/B12/B6/B2 is a vitamin Methylfolate/B12/B6/B2 is a vitamin

combination. It provides nutritional combination. It provides nutritional combination. It provides nutritional combination. It provides nutritional supplementation for certain nutritional supplementation for certain nutritional supplementation for certain nutritional supplementation for certain nutritional requirements.

requirements.requirements. requirements.

Sold under multiple names. Sold under multiple names. Sold under multiple names. Sold under multiple names.

FDA approved Deplin for augmentation FDA approved Deplin for augmentation FDA approved Deplin for augmentation FDA approved Deplin for augmentation For use with clients that have low plasma For use with clients that have low plasma For use with clients that have low plasma For use with clients that have low plasma

and/or low blood cell folate and/or low blood cell folateand/or low blood cell folate and/or low blood cell folate

Exposure to light that is brighter than indoor light but not as

bright as direct sunlight.

Do NOT use ultraviolent light, full-spectrum light, heat lamps

or tanning beds.

Use light for 30 minutes to 2 hours per day, usually first thing

in the morning is best time.

Response occurs in 2-4 days, for SAD up to 3 weeks Used for SAD, jet lag, and sleep disorders.

Replaces lost sunlight exposure and resets circadian rhythms

(biological clock).

Most common side-effects: eyestrain, headaches, nausea,

sweating, agitation of feeling “weird”, if sensitive eyes or skin avoid this.

Tricyclics:

Tricyclics:

Tricyclics:

Tricyclics:

They inhibit the uptake of the

neurotransmitters: serotonin, norepinephrine and dopamine.

Peak concentrations achieved in 2-8 hours

but may extend to 10-12 hours.

Can take 10-14 days to get a full

therapeutic dose and six weeks for full effect.

(8)

Elavil (Amitryptline) Strong sedative Tofranil (Imipramine) Moderate sedative Pamerlor/Aventyl (Nortriptyline) Mild sedative 150-300mg a day 150-300mg a day 75-150mg a day

Can complicate heart problems, sweating,

dryness of the mouth, headache, increased appetite for sweets, weight gain, unpleasant taste, difficulty urinating, change in sexual desire and ability, decrease, muscle twitches, fatigue, and weakness.

Can interact with: thyroid hormones,

anti-hypertensive medications, oral contraceptives, blood coagulants, sleeping medications, anti-psychotics, diuretics, antihistamines, aspirin, bicarbonate of soda, vitamin C, alcohol and tobacco.

These drugs work by blocking

the enzyme monoamine

oxidase.

These medications work by

prohibiting the breakdown of

key chemicals in the brain,

including norepinephrine.

*MAO inhibitors have a high potential for interacting with other drugs. Many dietary restrictions: No foods with the chemical tyramine (e.g., cheese, beef or chicken liver, pickled herring, red wine, chocolate, coffee, raisins, pineapple and bananas.)

Eating these foods that have a high amount of the amino acid tyramine. The body cannot break it down and the tyramine pushes the increased norepinephrine (sort of like adrenaline) in the blood stream, blood pressure increases with possible stroke and death.

Marplan (Isocarboxazid) 30-50mg

Nardil (Phenelzine) 45-90mg a day

Eldepryl (Selegiline) 20-50mg

Parnate (Tranylcypromine) 30-50mg

Aurorix (Moclobemide)*

(9)

Dizziness, rapid heart rate.

Interaction potential with certain foods

(watch out for monosodium glutamate, MSG).

Can interact with OTC cold and allergy

preparations, antihistamines,

amphetamines, insulin, narcotics, anti-Parkinson medications.

Reactions may not appear for several hours

and can include: rapid heart rate, high blood pressure, seizures, stroke and/or coma.

Prozac (Fluoxetine) Zoloft (Sertraline)

Paxil (Paroxetine) - Do not use with MAO

inhibitors- stronger birth defect warning for 2006 (congenital malformations) not recommended in 1st

trimester.

Luvox (Fluvoxamine) Celexa (Citalopram)

Lexapro (S-citalopram) this medication is used for

Depression, Dementia, Panic Disorder and GAD Listed by brand name first)

Some examples: Prozac, Celexa and

Zoloft

Clients report strange and variable

side-effects such as extremely tired,

horrible hang-over, even with one

glass of wine

Always go slow and try a very little

amount first to see if there is a

reaction

SSRIs alone put individual at small risk of

stomach bleeding

Aspirin and Ibuprofen can damage the

damage the stomach lining

Risk increases significantly when these drugs

are mixed

For pain consider acetaminohen

Paxil appears to negate the effects of the

cancer drug given primarily to women who have tumors that respond to estrogen

Paxil inhibits the metabolism of the other

drug preventing it from breaking down into a more active component

Safer SSRIs that are less likely to interact are:

(10)

Effexor (Venlafaxine HCL) - 75mg a day in 2 or 3

equal doses-SNRI

Wellbutrin (Buprorion) Watch high dose never

exceed 450mg a day

Remron (Mirtazpine)

Reboxetine

Cymbalta (Duloxetine) –nerve pain in diabetes Prestiq (Desvenlafaxine)-SNRI

Effexor and Effexor XL

Effexor must not be used concomitantly in patients taking MAOIs or in patients who have taken MAOIs within the preceding 14 days due to the risk of serious, sometimes fatal, drug interactions with SNRI or SSRI treatment or with other serotonergic drugs.

These interactions have been associated with symptoms that

include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma.

Based on the half-life of venlafaxine, at least 7 days should

be allowed after stopping Effexor before starting an MAOI.

Be careful of overdose (especially when used

with alcohol)

Should be prescribed in smallest quantity

available

Manufacturer Wyeth has but out over-dose

information because of higher risk of death when compared to those on SSRIs and lower risk when compared to tricyclics

Watch for tachycardia, changes in level of

consciousness, seizures, vomiting and liver necrosis, serotonin syndrome and death.

Wellbutrin affects dopamine levels if you have

a history of seizures this magnifies risk of having seizures

Without seizures if you increase normal daily

dose you can also have increased risk of developing them (2x normal daily dose increases risk tenfold)

Approved for:

Depression,

Generalized Anxiety Disorder, diabetic nerve pain, and fibromyalgia

Works with Serotonin and norephinephrine

Monitor when starting therapy closely for

new or worsening depression symptoms, suicidal thoughts or behavior, or unusual changes in behavior.

Cymbalta is not approved for use in

patients under age 18.

No increased risk has been shown for adults

over age 24, and risk decreased for those over age 65.

Do not take with MAO’s or Mellaril

(11)

watch for new or worsening symptoms, unusual changes in behavior,

thoughts of suicide, anxiety, agitation,

panic attacks,

difficulty sleeping, irritability, hostility, aggressiveness,

impulsivity,

restlessness, or extreme hyperactivity.

restlessness, agitation, dizziness, dry

mouth, difficulty sleeping, headache, nausea, vomiting, constipation, change in weight, tremor, confusion, rash, itching, seizures, sexual disinterest, possible weight gain, suicide potential, postural

hypotension, possible fertility decrease. Do not use these medications with a MAO inhibitor.

Symbyak Symbyak Symbyak Symbyak (olanzapine and (olanzapine and (olanzapine and (olanzapine and

fluoxetine HCl) fluoxetine HCl) fluoxetine HCl) fluoxetine HCl)

Uses the “big three”

neurochemicals Approved for treatment of bipolar depression Combines active ingredients of Zyprexa and Prozac

Should start to feel

better in one week, keep getting better if on it longer

No Mellaril No MAOs Not for use with

Dementia Psychosis

Not approved for use

with children

Beware of mixing SSRIs (e.g., Prozac, Paxil,

Zoloft or Lexapro) with the family of migraine drugs known as Triptans (e.g., Imitex, Imigran [sumatriptan-injection], Zomig [zolmitriptan], Amerge, Narmig [naratriptan] and Maxalt [rizatriptan]

Both drugs cause increase in serotonin levels

can cause “serotonin syndrome”

Symptoms include: diarrhea or nervousness

to increased heart rate, seizures, rare cases death

Traditional Chinese Medicine

(TCM) – uses herbs, acupuncture,

acupressure (shiatsu, tsabu, jin

shin, jujitsu), and physical

exercise like t’ai chi chian or

qigong

(12)

Ayurveda– uses pranayama (alternate

nostril breathing),

Abhyanga (rubbing skin with oil, usually

sesame),

Rasayana (herbs and mantras during

meditation),

Yoga, panchakarma (intense cleansing

therapy including diaphoretics, diuretics, cathartics, and emetics), and

Herbal remedies

Hypnotherapy– technique of focused

attention; especially helpful for pain management, addictions, and phobias

Biofeedback– relaxation technique to enable

people to gain control over autonomic responses, such as heart rate, blood pressure, and voluntary muscle contractions

Relaxation Techniques– autogenic training,

progressive muscle relaxation, meditation

lymphatic massage,

neuromuscular (deep tissue)

massage,

rolfing (fascial manipulation)

Reiki– practitioners place their hands lightly

on or just above the person with the goal of facilitating the person’s own healing response

Acupuncture– use of needles placed along

the meridians to relieve symptoms of many diseases

Healing touch– practitioner identifies

imbalances and corrects a client’s energy by passing his/her hands over the patient

Millimeter wave therapy (MW)– low-power millimeter wave irradiation used to treat skin diseases, aid in wound healing, relieve symptom related to cancer GI and cardiovascular diseases, and psychiatric illnesses

Sound energy therapy– music therapy, wind chime and tuning fork therapy; used to relieve pain and anxiety

Chamomile Feverfew Ginger Kava Lavender SAMe St John’s Wort Valerian

(13)

Methadone and

antidepressants should

never be mixed as each

drug increases the sedative

properties of the other

The power of caffeine

and alcohol.

Anything Strong Enough to Create an Action,

is CLEARLY Strong Enough to Create a Reaction.

There are no “quick fixes.”

References

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