Psychiatric Disorders and Pharmacology

Mood Disorders 

Major Depression (MD)

• Theories of Cause 
1. o Genetic: Genes play role but must interact w/environment to develop MD 
2. o Biochemical: Initially thought path dysfunction of serotonin (regs sleep, appetite, libido) and norepi (energy, pleasure, concentration) cause; But prob also i/c dopamine, Ach, Gaba; Also probably not sole cause 
3. o Hormonal regulation: Hypo-Pit-Adrenal path malfunction →↑ cortisol which is often high in depressed pts 
4. o Circadian rhythm: Most pts w/MD have loss of deep and REM sleep 
5. o Psychodynamic: Stressors and events trigger episode if vulnerable 
6. o Cognitive: Experience teaches negative thoughts which → depression; Three learned thoughts responsible: 1) Negative self view, 2) Pessimistic view of world, 3) No hope for future 
7. o Learned Helplessness: Normal anxiety is replaced by depression as person learns they have no control over situations; Popular modern theory that believes remedy is teaching coping skills and self confidence (i.e. groups) 
• Facts: *Pt presents w/history of one or more major depressive events and NO manic/hypomanic episodes; *s/s represent a change in usual behavior (slight difference from dysthymia); *Usually have more than one episode in life; *Not verbally mediated; *One episode means meds for life 
• DX: 5 or more of following occur daily for 2 wks: 1) Depressed mood most of day, 2) Anhedonia, 3) Wt loss (5% in month), 4) Insomnia/hypersomnia, 5) ↑or↓ motor activity, 6) Anergia, 7) Feel worthless or guilty, 8) indecisive or ↓ concentration, 9) Death/suicide thoughts 
• Subtypes: MD may include following features: Psychotic (halluc/delusions), Catatonic (echo, strange movement), Melancholic (wt↓, early morn wake), Postpartum onset (4 wks PP), Seasonal (winter), Atypical (wt↑, oversleep) 
• NX: Severe vegetative (∆ in activity necessary to support life) s/s include: severe wt↓, psychomotor retard, early morn waking, ↓ libido; Main NX DX: ↑ suicide risk after few days on meds during cycle out, ↓ coping, ↓ self carev Monitor sleep, wt/eating, bowel movements; Expect withdrawn behavior; Usual TX for MD is Cognitive behavior therapy and ECT (NPO 6hr prior; remove contacts, dentures; Give premeds 30 min prior)

Dysthymia

• Facts: S/S represent usual behavior for 2 yrs; Less severe low, verbal mediate 
• DX: 2 or more of: 1) ↑or↓ appetite (often ↑), 2) ↑or↓ sleep, 3) Anergia, 4)↓self-esteem, 5) Poor concentration/decision making, 6) hopelessness 

Bipolar Disorders

• Facts: Chronic, recurrent shifts in mood, energy, and functioning; Severe mortality w/highest suicide rate of all Psych illnesses; Often starts at 20 yrs; Probable genetic influence as bipolar pts often have bipolar relatives 
• Type 1: At least one Manic episode alternating with MD 
• Type 2: At least one Hypomanic episode alternating with MD (often OCD) 
• Cyclothymia: Hypomanic episode alternates with minor depression (2 yrs) 
• Psychotic: Severely impaired mental state w/hallucination, delusion, and/or personality ∆, w/disorganized thought and loss of touch w/reality; Emergency! 
• Mania: ↑ impairment in activity/relationships; TX needed to avoid harm to self/others; Psychotic features; S/S not due to drugs/disease 
• Hypomania: ∆ in functioning/mood that is not ordinary for pt and can be observed by others, no impairment socially, S/S not due to drugs/disease, TX not an emergency 
• Bipolar DX: Distinct abnormal/persistent ↑ in mood for 4 d (hypo) or 1 wk (mania), AND 3 or more of: 1) Grandiosity, 2) ↓ need for sleep (rested w/3 hrs), 3) ↑ need to be talkative, 4) Flight of ideas, 5) Distractible, 6) ↑ goal-directed activity, 7) ↑ need for unhealthy living (↑ spending, sex) 
• Bipolar episodes: Mixed (↑ and ↓ daily for 1 wk); Rapid Cycling (4 or more episodes in 1 yr); Regular (at least 1 manic episode w/depression) 
• Mental Status Exam: Depending upon manic (↑) vs depressed (↓) will show: Appearance (↑ bizarre dress, frequent ∆; ↓ poor hygiene); Speech (↑ flight of ideas, rapid; ↓ retarded); Thought (↑ grandiose, distracted; ↓ hope/helpless); Affect (↑ labile; ↓ flat/dull); Psychomotor (↑ hyper; ↓ retarded); Delusions (↑ grandeur, bizarre; ↓ negative triad); Hallucinations (any in both states) 
• NX: Don’t let make big decision when ↑ or ↓; Extreme risk of self harm; Electroconvulsive therapy possible (for psychotic depression); Sleep therapy; Distractibility can be used positively during interventions; ↓ environmental stimulus (such as neutral colored rooms, coordinated accessories) 

Mood Disorder Pharmacology 

Antidepressants (MD pts)

• Facts: All but MAOI block reuptake of serotonin and sometimes norepi making more available in synapse (↑ mood, ↑ alert, ↑ concentration); Can be given once a day, but often has 3-4 wk time to therapeutic effectiveness 
• Indications for use: Recurrent depression, Psychomotor retardation, Depression w/no clear cause, Family Hx, Chronic pain, Eneuresis 
• Types 
• Benzodiazepines
• Alprazolan (Zanax): Short term only as ↑ dose needed over time
• SSRI (selective serotonin reuptake inhibitor) 
• SSRI S/E: Sexual depression/dysfunction, N/V/D, insomnia, anxiety, dry mouth, tremor, fatigue, H/A, toxic s/e rare 
• NX: Never take w/MAOIs, Liver/renal/CBC test, d/c meds slow 
• Fluoxetine (Prozac): ↓ sedation, ↓ S/E
• Sertraline (Zoloft): ↓ toxicity in OD, ↓ S/E, ↓ halflife than Prozac 
• Paroxetine (Paxil): Safest for elderly, Lowest halflife 
• Fluvoxamine (Luvox) ƒ Citalopram (Celexa) 
• Escitalopram oxalate (Lexapro)
• SNRIs (Serotonin/Norepinephrine reuptake inhibitor) 
• Pros: ↓ sex probs, ↓ insomnia, response quicker, anxiolytic like 
• Cons: ↑ BP, Sedating, Anticholinergic s/e (constipation, sweat) 
• Effexor (Venlafaxine): S/E: dizziness, migraine, wt gain 
• Serzone 
• Trazodone (Desyrel) 
• Remeron: S/E: somnolence, dizzi, wt gain; Adverse: agranulocytosis, neutropenis; NX: some respond well only to this
• Norepi/dopamine agonist 
• Facts: Stimulant inhibits reuptake and ↑ release of Norepi/dopa 
• Cons: ↑ seizure risk ƒ Bupropion HCl (Wellbutrin): No effect on serotonin/ MAO 
• Tricyclics (Norepi/serotonin reuptake inhibitor + minor Ach/Hista effect 
• Examples: Imapramine (Tofranil), Desipramine (Norpramine, Pertofrane), Amitriptyline (Elavil, Endep), Nortriptyline (Pamelor, Aventyl), Protriptyline (Vivactil), Doxepin (Sinequan)
• S/E: Anticholinergic effects (dry mouth, constipation, urinary hesitant/retention, sweating, drowsiness, blurred vision); EPS Cardiovascular (postural ↓ BP, ↑ HR, heart conduction probs); Glaucoma worsened, Toxic confusion/psychosis; Wt gain, SZ,
• Overdose: 1000-4000 mg can be Fatal
• MAOIs 
• Facts: Monoamine (epi, norepi, sero, dopa) oxidase responsible for destroying excess/used MAs; Inhibiting enzyme ↑ level of all 
• Types: Phenelzine (Nardil), Isocarboxazide (Marplan), Tranylcypromine (Parnate)
• CX!: Some foods contain MAs (tyramine) which if not metabolized in liver causes ↑↑ HT and CVA; Foods include aged cheese, chicken liver, beer, red wine, chocolate, cold/sinus meds, diet pills; Avoid certain restaurants (Chinese); 1o s/s is severe h/a
• S/E: ↓BP most critical; Orthostatic ↓BP, dizziness, ↑ appetite 
• Key: ↑ BP is toxic effect (wrong food); ↓ BP is med caused S/E
• Psychostimulants 
• Facts: Meds such as Ritalin, Dexedrine, Adderall, and Cylert can be used sparingly in depression; Block reuptake and ↑ production 

Mood Stabilizers (Bipolar 1 pts)

• Lithium 
1. Facts: Used in psychiatric disorders non-responsive to other meds; Blood level of 0.1-1.5 key as toxic death possible. Higher only w/psychosis; Must maintain adequate salt in diet (consistent level, not too ↑ or ↓) 
2. Indications: Acute Mania, Bipolar prophylaxis 
3. Possible use: Bulimia, Alcohol abuse, Schizoaffective (mania or depression with schizo like delusions/hallucinations/etc) 
4. Method of action: Replaces Na+ in many neurons but creates different resting potential, limiting speed of nerve impulse = ↓ mania/hyperactive 
5. S/E: Major risk of hypothyroidism and urine concentration probs; Parkinson like, cog wheeling, sluggish, forgetful; Chronic N/V/D so take w/food; Wt gain, Polydypsia, Polyuria, Allergic rash w/capsules 
6. C/I: Never take with diuretics or Anticholinergic meds 
7. Causes of toxic levels: ↓ Na intake (more room for Li); Sweating, Illness 
• Anticonvulsants 
• Carbamazepine (Tegratol): Used when no response to Lithium; Better for rapid cycle Bipolar; Blood levels at 6-8 mg/l
• S/E: Sedation, Mal coordinated, agranulocytosis, aplastic anemia so NX: monitor CBC and alert for fever/sore throat; birth defects
• Valproate (Depakene, Depakote): Used w/manic or schizoaffective; Blood levels at 50 mg/l
• S/E: Severe/Fatal Hepatotoxicity, ↓ platelets, neural tube defects
• Clonazepam (Klonopin): Benzo for acute mania, acute help while waiting for Lithium effects to occur ƒ S/E: Sedation, Anoxia, Disinhibition effect

Schizophrenia 

Facts: Psychotic Disorder (other PDs are schizoaffective, delusional, induced psychosis); Drug abuse (50%), nicotine addiction (90%) common; ↑ cause of death is suicide

Theories: Dopamine, Serotonin, and Norepi elevation is suspected but no concrete proof exists; Genetics plays role (45% chance with schizo twin or schizo parents) and with environmental factors is possible cause; MRI shows enlarged ventricles

4 steps to DX: (must meet all 4 for schizo dx)

• Characteristic S/S, active phase: 2 or more of following in 1 month period: 1) Delusions, 2) Hallucinations, 3) Unorganized speech, 4) Catatonic behavior 5) Negative symptoms 
• IF: (bizarre delusions or auditory hallucinations) AND (continuous voices or multiple voices) is enough to satisfy first step 
• Social Dysfunction: Marked decline in social abilities (work, relations, self-care, etc) or failure to achieve expected level in adolescence 
• Duration: Continuous s/s for 6 months w/at least 1 month of active phase s/s 
• Rule Outs: Other mental diseases and medical conditions have been r/o; If pt has developmental disorder then must present w/ prominent hallucinations or delusions for 1 month for schizo dx 

Symptom Groups (which ones are present varies between individuals)

• Positive: 
1. Acute onset, Normal CT/neuro tests, Good response to antipsychotic meds 
2. Types: Hallucinations, Delusions, Unorganized speech, bizarre behavior, Ideas of reference delusions (others are plotting against me) 
• Negative: 
1. Insidious onset, CT shows atrophy, abnormal neuropsychological tests, Poor response to antipsych meds, More destructive than positive s/s 
2. Types: Blunt affect, Poverty of thought (alogia), ↓ motivation (avolition), Inability to experience pleasure (anhedonia) 
• Cognitive: Inattentive, Distractible, Poor memory/problem solving/decisions, Illogical thinking, Impaired judgement, Can’t name familiar objects 
• Mood: Dysphoria, Suicidal, Hopelessness 

Subtypes: Paranoid, Catatonic, Disorganized, Undifferentiated, Residual

Course of Disease: Prodromal s/s may appear up to 1 yr prior to first psychotic break

and include withdrawal, lonely, depressed, unrealistic future plans; Early phase s/s include anxiety, phobias, obsessions, compulsions, concentration/schoolwork probs 

NX: For auditory hallucinations, pt should tell voices to go away; for poisoning suspicion the nurse can taste food in pts presence,

Schizophrenia Pharmacology 

Facts

• Inhibit neurotransmitters dopa, serotonin, norepi, histamine to ↓ psychosis 
• S/E: Dop antagonist (parkinsonism, akinesia, akathisia, dyskinesia; (↑prolactin/amen/galactorhea) ACH antag (Blurred Vision, dry mouth, constipation, urinary hesitancy) Norepi antag (orthostatic hypotension, ejaculation probs) Hist antag (wt gain, sedate); Atropine Psychosis (Dry, Fever, Confused, Diplopia)

Atypical Antipsychotics:

• Facts: Target (+) and (-) schizo signs w/few S/E b/c Dop antag only in limbic 
• Olanzapine: S/E wt gain, ↑ CHO, DM 2 (best at improving cognition) 
• Clozapine (Clozaril) S/E can be ↓ WBC so NX CBC weekly for 6mos; S/E: sedation, ↑salivate, tachycard, dizzi; b/c of effects NOT 1st CHOICE 
• Risperidone (Risperdol) Does not ↓ WBC but at dose just above normal causes motor probs; S/E: Sedates, orthohypo, wt gain, sex probs, ↑ CVAs; Only Atypical available in Depot Form (oil based time released SQ) 
• Quetiapine (Seroquel) Broad antagonist especially Norepi/Hist (see S/E in 1st gen); Very few extrapyramidal symptoms (movement probs) 
• Ziprasidone/Geodon (sero/norepi reuptake inhibitor; s/e ↓BP, ↑QT interval so fatal with arrhythmias, EKG and K/Mg test prior to Rx) 
• Aripiprazole/Abilify (↓ dopa levels where high and ↑ dopa levels where low, s/e sedate, ↓ BP, anticholinergic) 

Traditional Antipsychotics

• Facts: Pros: Cheap, Depot form (oil based time released SQ) Cons:Dopa receptor block in limbic/motor areas which can cause severe EPS s/e! 
• EPS: extrapyramidal s/s: Akisthesia (restless feet), Dystonia (muscle spasm), Akinesia (heavy limbs), Parkinson like, Tardive dyskinesia (face muscle spasms) 
• o Anti-EPS: Common meds for EPS tx are Benadryl, Cogentin, Artane
• Common Types (Phenothiazines except Haldol, a Butyrophene) 
• Haloperidol (Haldol): ↓ sedation, ↑ doses used to ↓ aggressive behavior, ↑ risk of EPS, ↓ hallucinations, ↓ hypotension risk, used w/elderly
• Chlorpromazine (Thorazine): ↑ sedation, ↑ hypotension risk, ↓ EPS risk 
• Thiorizidine (Mellaril): Severe ECG ∆s, sudden death, Last resort med 
• Trifluoperazine (Stelazine): low sedation, used with withdrawal/paranoia 
• Fluphenazine (Prolixin): Very little sedation