Steven Smith, NP Montgomery, Alabama CONFLICT OF INTEREST STATEMENT: Steven Smith, NP has in years past been on the speaker bureau for Pfizer Inc though not currently. This CE activity was compiled without the aid of any pharmaceutical company. The medications and products mentioned in this activity will be presented in a fair and balanced way. No ink pens or coffee cups were received in exchange for endorsement of any pharmaceutical product mentioned in this presentation. WHAT IS FIBROMYALGIA SYNDROME? Is it a musculo-skeletal disorder? WHAT IS FIBROMYALGIA SYNDROME? Is it a musculo-skeletal disorder? Is it a mental condition or is it all in their heads? WHAT IS FIBROMYALGIA SYNDROME? Is it a musculo-skeletal disorder? Is it a mental condition or is it all in their heads? Is it an inflammatory, rheumatologic problem? WHAT IS FIBROMYALGIA SYNDROME? Is it a musculo-skeletal disorder? Is it a mental condition or is it all in their heads? Is it an inflammatory, rheumatologic problem? Is it an illness of the central nervous system? FMS is thought to be an illness of the CENTRAL NERVOUS SYSTEM And even more, an illness of the NEURO-ENDOCRINE SYSTEM FMS is thought to be one of the many CENTRAL SENSITIZING SYNDROMES What is CENTRAL SENSITIZING SYNDROME? Afferent (conducting inward) sensory input into THE DORSAL HORN GANGLION of the spinal column overwhelm the GATED PROTECTIVE MECHANISMS so that you get a WIND-UP PHENOMENON. What is a WIND-UP PHENOMENON? It is NEURON HYPEREXCITABILITY with a LOW DISCHARGE THRESHOLD that worsens with each sensory input (pain, touch, movement, any sensory input). This creates an EXAGERATED DISCOMFORT in people with CENTRAL SENSITIZATION SYNDROME. FMS is thought to be one of several CENTRAL SENSITIZING SYNDROMES. Others include: IRRITABLE BOWEL SYNDROME IRRITABLE BLADDER SYNDROME CHRONIC PELVIC PAIN CHRONIC FATIGUE SYNDROME CHRONIC T M J CHRONIC HEADACHE RESTLESS LEG SYNDROME THERE IS OFTEN OVERLAP AMONG THESE CONDITIONS Also overlapping with FMS are a higher prevalence of coexisting psychopathology: Depression GAD/Panic Disorder PTSD Bipolar Disorder Insomnia OCD (responds best to FMS Tx) (responds worse to FMS Tx) (responds worse to FMS Tx) Pain pathways are a two-way street. There are AFFERENT, conducting inward, ascending pain pathways, (Pain towards the brain) or (Pain on a train trying to gain toward the brain) AND Ameliorating, inhibitory, descending pain pathways. (Drain the pain from the brain) or (Train the pain to wane) Some of the neurotransmitters involved in the ASCENDING pain pathways are: Substance P Glutamate and other excitatory amino acids Neurotrophins Nerve Growth Factor Brain Derived Neurotrophic Factor These are found in higher levels in the CEREBRAL SPINAL FLUID of patients with Fibromyalgia Some of the neurotransmitters involved in the DESCENDING pain pathways that inhibit pain are: Norepinephrine Serotonin The metabolites of these were found to have LOWER levels in the Cerebral Spinal Fluid of patients with Fibromyalgia. ! WAIT ! I THOUGHT PAIN WAS A BRAIN THING In one FMS study, they apply painful stimuli to both FMS patients and a normal control group while performing an MRI observing the increased activity in the areas of the brain related to pain. It took only half of the painful stimuli to light up these brain areas in the FMS patients than the control group. The FMS patients have an increase in the “gain” or sensitivity on their CB radios OR have an increased volume control on their MP3 players of pain. So, what does this have to do with PHARMACOLOGY? To treat FMS appropriately, you must understand: 1. The Neurotransmitters you want to increase and decrease. 2. The Receptors you want to block. 3. The Neurons that you want to control hyperexcitability. 4. The ascending, descending, and brain pathophysiology of the CNS of the FMS patient. If you understand this you will also understand what pain ameliorating therapies NOT to use. TWO GREAT TRUTHS You will not adequately treat what you cannot diagnose. Richard Sobel, MD, mentor If you do not know how to diagnose Fibromyalgia then this pharmacology lecture is useless. Steven Smith, NP, mentee FIBROMYALGIA is a diagnosis of EXCLUSION. That is why FMS is a “Syndrome” and not a “Disease”. There is no specific test for FMS. Diagnosing FMS take the good old fashioned hard work of a good HISTORY AND PHYSICAL EXAM (i.e.. SOAP) HISTORY AND PHYSICAL EXAM S. CC, HPI, PMH, SocH, PsychH, FH, ROS O. PHYSICAL EXAM, DIAGNOSTIC TESTS A. ASSESSMENT/DIAGNOSIS P. PLAN Name: _________Date:_______ Age:_39_Sex: __F__ FMS affects 3 million to 8 million people in the U.S. Age is usually between 20 and 60 years old. Over 80% of those diagnosed with FMS are female. Mostly occurs in females of reproductive age. S - SUBJECTIVE CHIEF COMPLAINT: Rarely “I think I have 14/18FMS” More often: “I’m depressed” “I can’t sleep” “I’m tired all the time” AND “I hurt all over” Legitimizing statement: “I’m afraid I’m going to lose my job.” 20% apply for disability 50% leave the workforce HISTORY OF PRESENT ILLNESS FMS Onset/duration: “A while.” >3 mo. Location: “My neck and my back” 4quads Severity: “a 6 out of 10” Quality: “It’s hard to describe, it just hurts.” Modifying factors: “I was in a wreck 2 years ago.” “My friend was killed.” HISTORY OF PRESENT ILLNESS Modifying factors: “I was in a wreck 2 years ago.” “My friend was killed.” Modifying factors in FMS: Acute trauma Improper body mechanics, Abnormal posture Infection, Inflammation Psycho-social stressors Metabolic imbalance FMS HISTORY OF PRESENT ILLNESS Associated signs and symptoms: “I wake up tired”, “I’m depressed”, “My nerves are shot”, “I don’t sleep well”, “I’m gonna lose my job” Associated signs/symptoms in FMS: Cognitive impairment, poor sleep, fatigue, morning stiffness, anxiety, depression, impaired social function, impaired occupational functioning, sexual dysfunction HISTORY OF PRESENT ILLNESS Current Treatment: “Goody Powders didn’t help but I took a friends Lortab and it helped.” “I been on Prozac since my 1st marriage ended.” Treatment with FMS: Will NSAIDs help FMS? Will SSRIs help FMS? Will narcotics help FMS? CURRENT MEDICATIONS: Prozac 10mg qd Xanax 0.5mg BID Goody Powders CoQ 10 Will these help Fibromyalgia pain? PAST MEDICAL HISTORY: Fatigue, Trauma/MVA, Insomnia, Obesity PSYCH HISTORY: Generalized Anxiety Disorder Depression Abused by 1st husband Common comorbid psychiatric conditions with FMS: GAD, Depression, PTSD, Bipolar Disorder PAST SURGICAL HISTORY: C-Section x 2 Tubal ligation FAMILY HISTORY: Father: IBS Mother: Depression, Migraine 2 Children: ADHD There is a strong genetic predisposition for FMS with the other CENTRAL SENSITIZATION SYNDROMES (CSS) in family members. REVIEW OF SYSTEMS: Constitutional: Fever Fatigue Sleep apnea Weight change Energy level FMS No 70% Inactivity Down REVIEW OF SYSTEMS: Eyes: ENT: Pulmonary: Cardiovascular: FMS r/o inflam, neuro r/o infection r/o infection, asthma r/o CV disease REVIEW OF SYSTEMS: GI: Abd pain Constipation N/V/D Bleeding FMS 40% have IBS symptoms REVIEW OF SYSTEMS: GU: Dysuria/Frequency Incontinence Nocturia FMS r/o infection I.C. (CSS) r/o metabolic Ir. Bladder Sy. (CSS) REVIEW OF SYSTEMS: Musculoskeletal: Back pain Neck pain Arthralgias Myalgias FMS Always Always 80% 80% Fibromyalgia pain must be AXIAL not peripheral. Fibromyalgia pain must be in ALL 4 QUADRANTS, NOT unilateral, NOT upper or lower. REVIEW OF SYSTEMS: Skin: Rash Dry Skin Lesions FMS Butterfly/malar rash r/o Lupus Psoriasis/psoriatic Arth. r/o Thyroid Dz r/o cancer REVIEW OF SYSTEMS: Psychiatric: Depression Anxiety Insomnia Bipolar disorder FMS Highly coexistant Highly coexistant Highly coexistant Highly coexistant With FMS, 1st degree relatives of FMS patients are twice as likely to have a mood disorder. 1st degree relatives of FMS patients has an 8 fold risk of FMS or other CSS’s. REVIEW OF SYSTEMS: Neurological: Headache Paresthesias RLS CVA Seizures FMS 53% 35% 15% REVIEW OF SYSTEMS: Endocrine: Diabetes FMS Always r/o Thyroid Disease Always r/o Dyslipidemia ? Statins Vasomotor Perimenopausal Symptoms REVIEW OF SYSTEMS: Hemo/Lymph/Immun: Easy bruising/bleeding Lymphadenopathy FMS r/o cancer r/o cancer infection REVIEW OF SYSTEMS: GYN: Vag d/c Bleeding Pelvic Pain FMS r/o infection r/o pregnancy Other CSS’s are Chronic Pelvic Pain, Post C-Section Neuropathy, Post Inguinal Repair Neuropathy. Remember, damaged nerves can lead to a “wind-up phenomenum”. What is #1 cause of abd. Pain? O - OBJECTIVE PHYSICAL EXAM: Vital signs: Weight: Height BMI B/P HR RR Temp FMS 200 62” 37 138/88 92 16 98.2 ?fever PHYSICAL EXAM: Alert & oriented x3 Confused Clean Depressed Anxious FMS “Fibro fog 20%” ↓ Memory ↓ Attn. Span ↓ Task Switching ↑ with FMS & Chronic Pain ↑ Correlation PHYSICAL EXAM: Eyes: Conjunctiva FMS PERRLA r/o inflammatory Dz r/o anemia r/o MS EMOI r/o neuro problems ENT: r/o infection PHYSICAL EXAM: Neck: Supple LAD Thyroid FMS r/o infection r/o cancer r/o thyroid dz A GOOD TIME TO CHECK TENDERPOINTS SINCE MOST ARE AROUND THE NECK Bruits PHYSICAL EXAM: Respiratory: CTAB Effort normal Retractions Wheezing Crackles FMS r/o infection A GOOD TIME TO CHECK TENDERPOINTS AROUND THE BACK PHYSICAL EXAM: CV: FMS r/o fatigue cause ABD: r/o infection GU: GYN: RECTAL: r/o infection r/o infection (not a fibromyalgia tenderpoint) PHYSICAL EXAM: Lymph: Cervical Supraclavicular Axillary Inguinal FMS r/o infection & cancer A GOOD OPPORTUNITY TO CHECK TENDERPOINTS WITHOUT BEING TOO OBVIOUS PHYSICAL EXAM: Neuro: Motor Sensory FMS Weakness /?MS Reflexes r/o cervical, lumbar spinal stenosis r/o hypo/hyperthyroid Gait r/o MS, NPH, Parkinsn PHYSICAL EXAM: Musculo-skeletal: FROM Joints Swelling Erythema Laxity FMS Check joints for RA/OA Check tenderpoints PHYSICAL EXAM: Skin: Abnormal lesions Face Trunk Extremities FMS Rule out infection, lupus, psoriasis→(psoriatic arthritis) scleroderma, and other skin manifestations of other rheumatologic diseases that could cause FMS like pain. Location of FMS tender points: Attachment of neck muscles at the base of the skull Midway between neck and shoulder Muscle over upper inner shoulder blade 2 cms below side bone at elbow upper outer buttock Hip bone Just above knee on inside Lower neck in front Edge of upper breast bone DEMONSTRATION OF PHYSICAL EXAM WITH EMPHESIS ON FIBROMYALGIA TENDER POINTS NEED 11 OF 18 POSITIVE TENDER POINT FOR DIAGNOSIS OF FIBROMYANGIA FMS affects 2-3% of the general population of the US, 4% of the female population. The female to male “treatment seeking” ratio is 9:1 There is a 3 fold healthcare cost in FMS compared to an average American. SO, WHAT’S YOUR DIAGNOSIS SO FAR? 1. Family Hx of Central Sensitization Syndrome and Psychiatric conditions 2. She has an environmental trigger: MVA with friend killed 3. She has non-restorative sleep 4. She has a positive physical exam: 14/18 tender points MAYBE SHE HAS FIBROMYALGIA ! WHAT ARE YOUR DIFFERENTIAL DIAGNOSES? 1. Hormone imbalance: Hypothyroid, menstrual irregularities, adrenal insufficiency, DM 2 2. Infection: Post infectious fatigue (Mono), Chronic infection, Lyme Disease, HIV 3. Autoimmune D/O: Lupus, RA, PMR, Irritable Bowel Disease 4. Neurologic: Myasthenia Gravis, Multiple Sclerosis 5. Psychiatric Illnesses: Bipolar D/O, Substance abuse, eating d/o with malnutrition 6. Malignancies 7. Hypercalcemia (groans, stones, or bones) What diagnostic test do you need base on your DIAGNOSIS and DIFFERENTIAL DIAGNOSIS? Remember, FMS is a SYNDROME, a diagnosis of EXCLUSION. DIAG. TESTS RULING OUT U/A CBC Pregnancy Chem Pro ANA ESR RF CRP TSH CPK Kidney dz, DM, Infection Infection, anemia, ↓Fe, Cancer DM, Lyte Imbal., Hypercalcemia, Lupus Polymyalgia Rheumatica (PMR) Rheumatoid Arthritis Inflammation Hypothyroidism Polymyositis, Muscle Damage A - ASSESSMENT Diagnosis: FIBROMYALGIA - Has become the #1 pain syndrome in the US. GAD Depression Insomnia h/o neck/back injury (ALL CONTRIBUTORY) Obesity Tobacco abuse P – PLAN 3 Major Goals in the treatment of Fibromyalgia What are the 3 things you need to address and treat in anyone with any chronic pain? P – PLAN 3 Major Goals in the treatment of Fibromyalgia What are the 3 things you need to address and treat in anyone with any chronic pain? A. TREAT PAIN P – PLAN 3 Major Goals in the treatment of Fibromyalgia What are the 3 things you need to address and treat in anyone with any chronic pain? A. TREAT PAIN B. TREAT DEPRESSION P – PLAN 3 Major Goals in the treatment of Fibromyalgia What are the 3 things you need to address and treat in anyone with any chronic pain? A. TREAT PAIN B. TREAT DEPRESSION C. TREAT INSOMNIA P – PLAN THE TREATMENTOF FIBROMYALGIA INVOLVES: A. Treating Fibromyalgia Pain B. Treating Anxiety and Depression C. Improve Sleep Architecture P – PLAN THE TREATMENTOF FIBROMYALGIA INVOLVES: A. Treating Fibromyalgia Pain B. Treating Anxiety and Depression C. Improve Sleep Architecture A. TREATING FIBROMYALGIA PAIN Do you treat all pain the same? Chest wall pain NSAIDs Rib fracture Narcotics Gout Steroids, NSAIDs Migraine Triptans Post-op pain Narcotics DPN/PHN Antiepil., SNRIs,TCAs Or, you can shoot a fly with a shotgun and give them Lortab. NP’s are more sophisticated that that. (5 min. to prescribe narcotics, 30 min. to explain and treat without narcotics.) 3 TYPES OF PAIN 1. Peripheral Pain (Nociceptive): Rib Fx, OA/RA, Gout, Trauma, Post-op 2. Neuropathic (Damaged/entrapped nerves): DPN, PHN 3. Central Pain (Non-Nociceptive): FMS, IBS, Ch. Pelvic Pain, other CSS’s Can someone with RA, DPN, and drop a brick on their foot AND have Fibromyalgia at the same time? A. TREATING FIBROMYALGIA PAIN Because we now know more about the pathophysiology of Fibromyalgia pain, we will target our approach: 1. Target ASCENDING pain pathways 2. Target inhibitory, DESCENDING pathways Pain pathways are a two-way street. There are AFFERENT, conducting inward, ascending pain pathways, (Pain towards the brain) or (Pain on a train trying to gain toward the brain) AND Ameliorating, inhibitory, descending pain pathways. (Drain the pain from the brain) or (Train the pain to wane) A. TREATING FIBROMYALGIA PAIN 1. Target ASCENDING pain pathways. HOW? Decrease spinal neuron hyperexcitability with anticonvulsants a. α-2-δ (alpha-2-delta) ligand anticonvulsants 1. Pregabalin (Lyrica) – FDA approved for Fibromyalgia 2. Gabapentin (Neurontin) b. Other anticonvulsant/antiepileptic drugs How does pregabalin (Lyrica) and gabapentin work? They bind to the α-2-δ protein on the neuron that has voltage gated channels. A calcium ion has to go back through the gate before certain neurotransmitters can be released from the neuron. How does Pregabalin (Lyrica) and gabapentin work? (continued) If you decrease the influx of the calcium ions, you decrease the release of certain neurotransmitters into the synaptic gap, therefore decreasing the hyperexcitability of the neuron (seizure control) and, in this case, reduce the level of Substance P and Glutamate that play a role in pain processing and decrease the “wind-up phenomenum” in the pain sensing neurons. A. TREATING FIBROMYALGIA PAIN 2. Target inhibitory, DESCENDING pain pathways. HOW? a. Raise Serotonin-Norepinephrine levels 1. Serotonin-Norepinephrine Reuptake Inhibitors a. Venlafaxine (Effexor), Desvenlafaxine (Pristiq) b. Duloxatine (Cymbalta) – FDA approved for FMS c. Milnacipran (Savella) – FDA approved for FMS, inhibits Norepinephrine reuptake with a 3 fold higher potency that serotonin. A. TREATING FIBROMYALGIA PAIN 2. Target inhibitory, DESCENDING pain pathways. HOW? a. Raise Serotonin-Norepinephrine levels 2. Tricyclic Antidepressants (TCAs) a. Amitriptylline (Elavil) b. Nortriptylline (Pamelor) c. Imipramine d. Others A. TREATING FIBROMYALGIA PAIN 2. Target inhibitory, DESCENDING pain pathways. HOW? a. Raise Serotonin-Norepinephrine levels 3. Muscle Relaxers a. Cyclobenzeprine (Flexeril) A. TREATING FIBROMYALGIA PAIN 2. Target inhibitory, DESCENDING pain pathways. HOW? a. Raise Serotonin-Norepinephrine levels 4. Tramadol (Ultram, Ultram ER, Ultracet) – Has SNRI properties as well as weak μ (mu) opioid-receptor agonist properties 5. Exercise – Endorphins are pain inhibitors A. TREATING FIBROMYALGIA PAIN 2. Target inhibitory, DESCENDING pain pathways. HOW? a. Raise Serotonin-Norepinephrine levels HOW DO SNRIs WORK? Mechanism of action is unknown DESCENDING PAIN CIRCUITS Hypothalamus Periaquaductal Gray Rostral Ventral Medulla (serotonergic pathway) Dorsolateral Pontine Tegmentum (noradrenergic pathway) Dorsolateral Funiculus (SNRIs put the “Fun” in the Funiculus) A. TREATING FIBROMYALGIA PAIN 2. Target inhibitory, DESCENDING pain pathways. HOW? a. Raise Serotonin-Norepinephrine levels HOW? If you can reduce the re-uptake of these neurotransmitters back into the neuron, it leaves more neurotransmitter in the synaptic gap leading to pain inhibition, same as with the antidepressant/antianxiety effect of SNRIs. Pain pathways run through parts of the brain that tell us where the pain is and the intensity of the pain BUT, Some of the pain pathways run through the areas of the brain such as the amygdala that are related to the affective domain or the emotional response to pain. This leads us to the second aspect of the treatment of FIBROMYALGIA PAIN. P – PLAN THE TREATMENTOF FIBROMYALGIA INVOLVES: A. Treating Fibromyalgia Pain B. Treating Anxiety and Depression C. Improve Sleep Architecture B. TREAT ANXIETY AND DEPRESSION 1. Raise Serotonin-Norepinephrine levels a. SNRIs 1. Venlafaxine (Effexor) – Cheaper, generic 2. Duloxatine (Cymbalta) – FDA approved for FMS and anxiety and depression 3. Milnacipran (Savella) – FDA approved for FMS, inhibits Norepinephrine reuptake with a 3 fold higher potency that serotonin. You need the serotonin reuptake inhibition to treat anxiety. B. TREAT ANXIETY AND DEPRESSION 1. Raise Serotonin-Norepinephrine levels b. Tricyclic Antidepressants (TCAs) Remember: TCAs are too anticholenergic and sedation at high enough doses to treat anxiety and depression B. TREAT ANXIETY AND DEPRESSION 1. Raise Serotonin-Norepinephrine levels 2. Anti-Epileptic Drugs a. Pregabalin (Lyrica) – FDA approved for FMS, Seizure d/o,PHN, DPN, and in Europe approved for anxiety. b. Gabapentin (Neurontin) c. Valproaic Acid (Depakote) d. Carbamazepine (Tregretol) – both used for years for mood disorders B. TREAT ANXIETY AND DEPRESSION 3. What NOT to use: a. Benzodiazepines – They increase depression and increase pain scores. b. Narcotics – Kills a fly with a shotgun. Morpheus – the Greek god of dreams The Goal of Treating FMS: ECONOMIC 101 Try to get the pain scores from 6-7/10 to 2-3/10 so they can return to work so they can pay taxes. People addicted to benzos and narcotics tend to take more taxes than they pay in as a rule. P – PLAN THE TREATMENTOF FIBROMYALGIA INVOLVES: A. Treating Fibromyalgia Pain B. Treating Anxiety and Depression C. Improve Sleep Architecture C. IMPROVE SLEEP ARCHITECTURE 80% of FMS patients report Non-Restorative Sleep. Why do we want to improve sleep architecture? C. IMPROVE SLEEP ARCHITECTURE FMS polysomnographic studies show abnormalities in sleep continuity as well as sleep architecture. a. Decreased REM sleep with FMS b. Increased awakenings with FMS c. Abnormal alpha wave intrusions in non-REM which is found to worsen pain in sleep with FMS d. Stage 4 or Delta wave sleep is where many restorative hormones are activated like Growth Hormone. This leads to the fibrositis symptom complex causing non-restorative sleep. C. IMPROVE SLEEP ARCHITECTURE So, poor sleep increases pain and fibrositis symptoms. That is why Fibromyalgia is thought to be an illness of the NEURO-ENDOCRINE SYSTEM. C. IMPROVE SLEEP ARCHITECTURE 1. Antiepileptic Drugs – Improve pain and sleep a. Pregabalin (Lyrica) 1. Has a sedative effect 2. Enhances slow wave delta sleep b. Gabapentin (neurontin) C. IMPROVE SLEEP ARCHITECTURE 2. Tricyclic Antidepressants (TCAs) – Improve pain, depression and sleep. a. Amitriptylline (Elavil) b. Imipramine (Tofranil) c. Many others C. IMPROVE SLEEP ARCHITECTURE 3. Non-Benzodiazepine Sedatives – Improve sleep. a. Zolpidem (Ambien) b. Zaleplon (Sonata) c. Eszopiclone (Lunesta) d. DO NOT use benzo’s 4. Teach sleep hygiene 5. Treat depression and anxiety 6. Exercising/Stretching not within 3 hours of HS Which of the FDA approved medications would you want to start first? FMS pain with Fatigue dominant: Savella FMS pain with Depression dominant: Cymbalta FMS pain with Insomnia dominant: Lyrica P – PLAN THE TREATMENTOF FIBROMYALGIA INVOLVES: A. Treating Fibromyalgia Pain B. Treating Anxiety and Depression C Improve Sleep Architecture D. Other Nurse Practitioner Treatments D. Other Nurse Practitioner Treatments (that other healthcare providers probably won’t do) 1. Patient Education – Explain it 2. Instill a sense of self-worth 3. Avoid disability and narcotics 4. Establish anxiety reducing measures 1. Prayer 2. Exercise D. Other Nurse Practitioner Treatments 5. Exercising and stretching – Staying active 6. Address underlying psycho-social issues and stressors , Cognitive Behavioral Therapy (CBT) referral. 7. Medications 8. Referral – Physical Therapy, Rheumatologist, Neurologist, Pain Management 9. Hugs α-2-δ (alpha-2-delta) ligand anticonvulsants Adverse Reactions: Dizziness, somnolence, edema, weight gain Interactions: Potentiates other CNS drugs Precautions: Never stop AED’s abruptly Serotonin-Norepinephrine Reuptake Inhibitors Adverse Reactions: Nausea, somnolence/insomnia, constipation, dry mouth, hyperhydrosis, HTN Interactions: Other psych meds (MAOI, SSRI, Haldol) Precautions: Hypertension, Mania/Bipolar, Suicidal Ideation Tricyclic Antidepressants (TCA’s) Adverse reactions: Drowsiness, anticholinergic effects, Prolonged Q-T Interactions: Anticholinergics , Prozac, MAOIs, Alcohol/CNS depressants Precautions: SEIZURES, Hx of seizures, Increase fall risk and arrhythmias in Elderly, Urinary retention Tramadol (Ultra, Ultram ER, Ultracet, Ryzolt) Adverse Reactions: Dizziness, GI upset, Constipation, SEIZURES Interactions: MAOI, Carbamazepine, Alcohol Precautions: SEIZURES, concomitant use with opioids Non-benzo Hypnotics Adverse Reactions: CNS effects, Complex sleep related behaviors Interactions: Alcohol, CNS depressants (Marilyn Monroe effect) Precautions: Depression, Behavioral changes BIG PICTURE PRECAUTIONS SEIZURES: Tricyclic Antidepressants (TCAs), Tramadol, and bupropion (Welbutrin) lower the seizure threshold in people who may have never had a seizure. Caution using together. SEROTONIN SYNDROME: Keep in mind the doses of concomitant use of traditional SNRIs and other medications with SNRI effect like TCAs and Tramadol. No need to add an SSRI. QUESTIONS?