Treatment Of Schizophrenia

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Schizophrenia onset

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Early onset in adolescence/young adulthood

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Schizophrenia more common in

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men

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Schizophrenia Common presentation in

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teenage boys

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Prodromal period of schizophrenia

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s/s, withdraw and act "strange" isolate themselves, depression, loners then have 1st episode

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Schizophrenia Stage 1

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asymptomatic

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Schizophrenia Stage 2

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prodromal -negative s/s

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Schizophrenia Stage 3

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see positive s/s manifesting

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Schizophrenia Positive symptoms

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are those that most individuals do not normally experience but are present in people with schizophrenia. They can include delusions, disordered thoughts and speech, and tactile, auditory, visual, olfactory and gustatory hallucinations, typically regarded as manifestations of psychosis.[23] Hallucinations are also typically related to the content of the delusional theme.[24] Positive symptoms generally respond well to medication

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Schizophrenia Negative symptoms

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are deficits of normal emotional responses or of other thought processes, and respond less well to medication.[10] They commonly include flat or blunted affect and emotion, poverty of speech (alogia), inability to experience pleasure (anhedonia), lack of desire to form relationships (asociality), and lack of motivation (avolition).

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Schizophrenia Late onset more common in

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women

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Schizophrenia Late onset may have less prominent negative thinking, but definitely have

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bizarre delusions ; ex: aliens and poison gas) and auditory hallucinations

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Schizophrenia diff btwn bizarre and non-bizarre delusions?

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bizarre delusions (no content in reality- not feasible; ex: aliens planted chip in brain and poison gas in AC vents)

Non bizarre- people following, looking at me, talking about, ect- there is some basis in reality esp if dress weird

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Schizophrenia what is a delusion?

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false fixed belief or thought

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Schizophrenia what is a hallucination?

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is sensory related (smell, touch, hearing, seeing, ect)

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Schizophrenia Disturbance that must last for

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6 months or longer (1 month of delusions, hallucinations, or disorganized speech)

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5 dimensions of Schizophrenia

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1. Positive-
2. Negative-
3. Cognitive
4. Aggressive
5. Depression & anxiety-

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what are the positive dimensions of Schizophrenia

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1. Delusion (persecution is the most common), hyper religious, grandeur, thought broadcasting, thought insertion
2. Hallucinations- distorted sensory perception (auditory is the most common- ALWAYS screen or commands or dangers )

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what are the negative dimensions of Schizophrenia

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2. Negative- blunted facial affect, flattening, alogia (poverty of speech) , avolition (a psychological state characterized by general lack of drive, or motivation to pursue meaningful goals), apathy, antisocial, anhedonia, decreased ability to experience pleasure, don't want to participate in activities

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Sometimes we can get secondary negative sx's from?

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Medications

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Most common delusion

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persecution

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persecution

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people are out to get them or following them

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grandeur

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that they are Christ or a special being

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thought broadcasting

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thoughts are somehow known to other people

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thought insertion

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people are putting thoughts into their heads and controlling them

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most common hallucination? Always screen for?

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Auditory (sensory)
commands- these are dangerous!

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Cognitive dimension of schizophrenia?

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Cognitive- disorganized speech, language, odd views of language, impaired verbal fluency (most common)- cant produce spontaneous speech & engage in conversation

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Cognitive dimension of schizophrenia can be tested by 2?

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Phonologic fluency
Semantic fluency

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Phonologic fluency

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list all the words you can think of that begin w/ the letter G

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Semantic fluency

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I am going to give you a category (ex: fruits or animals) and I want you to list as many as you can

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Aggressive and hostile dimension of schizophrenia

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Overly hostile, Verbal and physical aggression Why we have ETO (emergency tx orders). Attempt suicide. Arson (do you ever feel like you want to burn things? Do you ever hurt animals?). Sexually acting out is very common. Why we have ETO (emergency tx orders)

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Depression & anxiety dimension of schizophrenia

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you can stabilize all other sx’s but they can get into depressive worry of everything still being terrible

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Typical antipsychotics- 1950's
AKA 3?

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“conventional”, first generation antipsychotics; neuroleptics- came about bc of the neurological Side affects

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Typical antipsychotics More effective in treating (know this)

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positive symptoms than negative symptoms

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potency of agents in typical antipsychotics

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High and low

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What is the Mech of Action of the Typical Antipsychotics?

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Dopamine 2 (D2) receptor blockade (antagonist)
Alpha adrenergic block- dizziness, sedation, low BP

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Schizo curable

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NO!

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These must be filled before there is a relief of symptoms of positive sx's

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65% of D2 receptors

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Stopping the meds abruptly (typicals)

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can worses S/S

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3 classes of Typical Antipsychotics?

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PHENOTHIAZINES
PIPERAZINES
BUTYROPHENONES

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Name the 2 PHENOTHIAZINES

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Thorazine
Mellaril (thioridazine)

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Typicals- Name the 2 PIPERAZINES

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Stelazine (trifluoperazine)
Prolixin (fluphenazine)*-

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Typicals- Name the 1 BUTYROPHENONES

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Haldol (haloperidol)*-

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1st developed*-

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Typical - PHENOTHIAZINE:
• Thorazine (chlorpromazine

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FDA indication for children- explosive & combative behavior (between 1-12 y/o)

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Typical - PHENOTHIAZINE:
• Thorazine (chlorpromazine

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Typical - PHENOTHIAZINE:
• Thorazine (chlorpromazine) high or low potency?

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Low potency (uses high mg)

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was largest selling- horrible sedation & weight gain. Eye toxicity.

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Typical - PHENOTHIAZINE:
Mellaril (thioridazine)

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used inpatient

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Typical - PIPERAZINES:
Stelazine (trifluoperazine)-

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has an IM formulation (12.5 mg q 2 weeks and pt can stay stable vs trying to get them to take PO med they won’t take); can be used off-label for children

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Typical - PIPERAZINES:
Prolixin (fluphenazine)*-

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can be used in children ages 3 and up; less orthostatic hypotensive effects and good for elderly

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Typical BUTYROPHENONES:
• Haldol (haloperidol)*-

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Haldol low or high potency?

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High potency meds (5 mg is very potent)

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2 typical antipsychotics FDA approved for use in children?

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thorazine & haldol

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Dopamine Hypothesis & 4 key dopamine pathways

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1. Mesolimbic dopamine pathway
2. Mesocortical dopmaine pathway
3. Nigrostriatal dopamine pathway
4. Tuberoinfundibular dopamne pathway

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Ex Q: Pt is showing s/s of involuntary tremors after staring TX w/ Haldol, which system is implicated?

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Nigrostriatal dopamine pathway

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Excess DA here results in POSITIVE symptoms

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Mesolimbic Pathway

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extends from ventral tegmental area of the brainstem to limbic area

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Mesolimbic Pathway

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Hyperactivity in this DA pathway mediates positive symptoms of psychosis

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Mesolimbic Pathway

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Responsible for positive s/s; excess DA circulating the brain

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Mesolimbic Pathway

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causes Auditory Hallucinations and delusions

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Mesolimbic Pathway

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Excess amphetamines (cocaine) can cause this as well

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Auditory Hallucinations and delusions

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D2 receptors mediate positive symptoms

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Mesolimbic Pathway

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Also reduce reward mechanisms causing apathy, anhedonia, decreased motivation, reduced interest and joy in social situations (secondary negative symptoms)

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Mesolimbic Pathway

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When D2 receptors are blocked, positive symptoms are reduced

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Mesolimbic Pathway

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mediate positive symptoms

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D2 receptors

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positive symptoms are reduced

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When D2 receptors are blocked

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Decreased DA here results in NEGATIVE symptoms (to pre-frontal cortex)

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Mesocortical Pathway

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Hypoactivity in this DA pathway mediates negative symptoms of psychosis

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Mesocortical Pathway

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D2 receptors blocked here where DA may already be deficient

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Mesocortical Pathway

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Neuroleptic induced negative syndrome” because these symptoms look so much like schizophrenia itself

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Mesocortical Pathway

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Deficits in DA result in MOVEMENT disorders (EPS, Parkinson’s disease)

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Nigrostriatal Pathway

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Basal ganglia is part of the extrapyramidal system

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Nigrostriatal Pathway

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part of the extrapyramidal nervous system

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Nigrostriatal Pathway

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D2 receptors blocked here produces a disorder of movement like Parkinson’s

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Nigrostriatal Pathway

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Sometimes called “drug-induced Parkinsonism” (start with pill-rolling of fingers)

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Nigrostriatal Pathway

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Motor side effects also called EPS (TD is irreversible!)

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Nigrostriatal Pathway

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Abnormal Involuntary Movement Scale (AIMS) used for this pathway

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Nigrostriatal Pathway

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– Increased Prolactin when DA is decreased or blocked (happens postpartum) happens here

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Tuberoinfundibular Pathway

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Artificially blocked pathway causes galactorrhea, gynecomastia, amenorrhea, impotence

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Tuberoinfundibular Pathway

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D2 receptors blockade may cause hyperprolactinemia here

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Tuberoinfundibular Pathway

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Prolactin- lab value to monitor (also seen w/ high doses of seroquel) in this pathway

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Tuberoinfundibular Pathway

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Associated with galactorrhea- secretion from the nipples (pathway)

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Tuberoinfundibular Pathway

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Associated with amenorrhea

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Tuberoinfundibular Pathway

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Amenorrhea may affect fertility

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Tuberoinfundibular Pathway

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Sexual dysfunction

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Tuberoinfundibular Pathway

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draw when a pt complains of milky nipple discharge

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Prolactin blood level

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Typical antipsychotics D2 receptors blocked in mesolimbic pathway

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reduces positive symptoms

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Typical antipsychotics D2 receptors blocked in mesocortical pathway can

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worsen negative symptoms (neuroleptic induced secondary symptoms)

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Typical antipsychotics D2 receptors blocked in nigrostriatal pathway can

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cause extrapyramidal symptoms

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Typical antipsychotics D2 receptors blocked in tuberoinfundibular pathway can

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cause hyperprolactinemia (sexual dysfunction & weight gain)

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D2 receptor antagonist; high potency drug

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Haldol (haloperidol)

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•**Can cause EPS, tardive dyskinesia, galactorrhea, and amenorrhea

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Haldol (haloperidol)

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Blocks alpha 1 adrenergic receptors

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Haldol (haloperidol)

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Usual dose range orally 1 to 40mg

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Haldol (haloperidol)

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Add cogentin for EPS; BNZ for akathisia

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Haldol (haloperidol)

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• Decanoate: up to one month effectiveness

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Haldol (haloperidol)

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Used as an ETO for violence/aggression

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Haldol (haloperidol)

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D2 receptor antagonist

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Prolixin (fluphenazine)

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EPS, tardive dyskinesia, increased prolactin

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Prolixin (fluphenazine)

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Add cogentin for EPS; BNZ for akathisia

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Prolixin (fluphenazine)

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Usual dose range orally 1 to 20 mg daily

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Prolixin (fluphenazine)

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IM: ½ the oral dose

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Prolixin (fluphenazine)

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Decanoate: every two weeks

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Prolixin (fluphenazine)

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An important diff btwn typical antipsychotics is that

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they were more effective in tx of + symptoms

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typical antipsychotics MOA

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block D2 receptors

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alpha adrenergic side effects

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low BP, dizziness, sedation

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D2 receptor antagonist and blocks alpha 1 adrenergic receptors

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Haldol (haloperidol)

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Typicals block up to what % of DA?

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90

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Pt shows signs of involuntary tremors after tx with Haldol, which system implicated?

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Nigrostriatal pathway DA is blocked.

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Pt c/o gynecomastia & gallactorhea, how do u figure out what pathway is involved? & what pathway is it?

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Draw Prolactin level, tuberoinfundibular

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The blockade of too much DA in this pathway tuberoinfudibular -would be associated with what side effects?

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gynecomastia
gallactorhea
amenorrhea
sexual dysfunction

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Muscarinic cholinergic blocking Side effects: 4

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dry mouth, blurred vision, constipation, and cognitive blunting

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Muscarinic cholinergic blocking DA and acetylcholine have a

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reciprocal relationship in the nigrostriatal pathway

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Muscarinic cholinergic blocking DA normally inhibits

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acetylcholine release

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Muscarinic cholinergic blocking DA is blocked, acetylcholine levels

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keep rising

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Muscarinic cholinergic blocking DA rises, it inhibits the ability for

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acetylcholine to be controlled

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Tremors are caused by too much

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acetylcholine

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When a DA receptor is blocked, acetylcholine activity

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increases because DA normally stops acetylcholine from being released

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When acetylcholine is overly active, this is associated with

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EPS

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Extra pyramidal side effects are the symptoms which occur in persons after taking

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anti psychotic medications. They are more commonly caused by the so-called typical anti psychotics but can also occur in all of them.

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extra pyramidal side effects: 4

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Tremor, akathisia, dystonia, rigidity

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haldol can be used to treat

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aggression, violent or out of control or ETO

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decreased DA= increased acetylcholine = EPS so treat with

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an anticholinergic (can cause urinary retention, hot, dry, blind, mad)

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If DA is blocked, it can no longer suppress acetylcholine release and acetylcholine becomes overly active causing

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EPS

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Conventional antipsychotics with what cause more EPS

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weak anticholinergic properties

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Blockade of histamine-1 receptors can cause

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weight gain and drowsiness

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Blockade of alpha-1 adrenergic receptors can cause

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orthostatic hypotension and drowsiness

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Cogentin is an

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anticholinergic to treat EPS

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If DA is blocked, it can no longer suppress

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Ach so Ach becomes overly active

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Compensation for over active Ach is to block it with an

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anticholiergic

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So if anticholinergic properties are available in the same drug such as an antipsychotic, it tends to have a lower ____

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EPS

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The use of an anticholinergic does not lessen the ability of a conventional (typical) antipsychotic to cause

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tardive dyskinesia

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Atypical antipsychotics (2nd generation) are

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(serotonin-dopamine antagonist) SDA

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Atypical antipsychotics (serotonin-dopamine antagonist)- can block and produce

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DA in certain areas;

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one DA receptor can have ____ receptors on it;

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5HT2A

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Antagonist:

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A substance that acts against and blocks an action. Antagonist is the opposite of agonist

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• Cause fewer extrapyramidal side effects

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Atypical antipsychotics (2nd generation)

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Are effective for negative and/or cognitive symptoms (old ones made s/s WORSE and old targeted the positive s/s)

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Atypical antipsychotics (2nd generation)

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Less increase in prolactin in the apppropriate pathway

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Atypical antipsychotics (2nd generation)

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Antagonize 5HT2 receptors

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Atypical antipsychotics (2nd generation)

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Reduce risk for tardive dyskinesia

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Atypical antipsychotics (2nd generation)

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% of DA blocked with typicals vs. atypicals

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90% typicals and 70% atypicals

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SDA means they are producing more _____ & _________

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seratonin and dopamine

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diff btwn typicals and atypicals:

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atypicals fewer side effects with EPS
newer targer both negative and + symptoms
old ones only targeted + sx and made flattening worse

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5HT2A antagonism Reduces

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Reduces negative symptoms

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Conventional antipsychotics do not have high affinity for

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5HT2A receptors

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5HT2A antagonism May improve positive symptoms

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by producing more seratonin

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– 5HT2A receptors also regulate

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glutamate release, by increasing it (hallucinations)

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5HT2A antagonism reduces

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glutamate, thus reducing positive symptoms

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5HT2A antagonism does what to prolactin?

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Reduces hyperprolactinemia

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5HT and DA have reciprocal roles in regulation of

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prolactin secretion: DA inhibits release; 5HT promotes release so the Basal ganglia- activity that might cause EPS is cancelled

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When D2 receptors blocked

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increase level of prolactin in this basal ganglia or tuber...

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When 5HT2A blocked

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no release of prolactin: one action cancels the other

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ORDER OF RISK OF WEIGHT GAIN: in atypicals 5

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1. Clozaril (clozapine) first - in 1990- worse
2. Zyprexa (olanzapine) in 1996- second worse; blocks a receptor in the brain that does not allow for them to feel full & they sleep A LOT! No hunger satisfaction w/ this new class of meds
3. Risperdal (risperidone) in 1994
4. Seroquel (quetiapine) in 1997
5. Geodon (ziprasidone) in 2001- 1st line for an obese person w/ DM (d/t less risk for weight gain)
6. Abilify (Aripiprazole) in 2002  not really in this class, in a class by itself d/t its MOA

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IF have pt compromised with type 2 diabetes which atypical would you consider starting 1st?

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Geodon bc of wt gain

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GOLD STANDARD! Used as a LAST resort- 3rd line TX bc of monitoring parameters. #1 best TX for refractory schizophrenia. Proven efficacy in TX resistant schizophrenia, shown to reduce SI in schizophrenia

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Clozaril (clozapine)-

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Clozaril (clozapine)- Symptoms can improve

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1 week (4-6 usual)

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Clozaril (clozapine)-

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Serotonin-dopamine antagonist (SDA)
• Symptoms can improve 1 week (4-6 usual)
• May reduce positive symptoms in those who do not respond to other antipsychotics
• Consider augmentation with valproate (depakote) or lamotrigine (lamictal)

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May reduce positive symptoms in those who do not respond to other antipsychotics (can have super responders)

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Clozaril (clozapine)-

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Clozaril (clozapine)- Consider augmentation with

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valproate (depakote) or lamotrigine (lamictal)

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Clozaril (clozapine)- So why don't we use it if it's that good?

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monitoring parameters

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Clozaril (clozapine)- monitoring parameters

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• CBC- @ baseline and weekly for 6 months
• Every other week for 6-12 months
• Every 4 weeks thereafter

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Clozaril (clozapine)- monitoring parameters if patient is taking clozapine after leukopenia

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Weekly WBC count for 12 months

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Clozaril (clozapine) • If discontinuing

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dose over 1 to 2 weeks; avoid abrupt discontinuation unless conditions warrant (leukopenia)

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Clozaril (clozapine)- Can have significant

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weight gain; monitor

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Can cause agranulocytosis, leukopenia, severe drop in WBC!!! If there is a drop

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Clozaril (clozapine)- STOP IMMEDIATELY!

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Clozaril (clozapine)- Titrating:
Typical dose

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at 12.5 mg x 3-7 days, increase 25-50mg/day q 3-7 days. Typical dose is around 450mg/day

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Zyprexa (olanzapine) 4

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• Can improve psychotic and manic symptoms within 1 week; may take several weeks for full effect on affective symptoms
• IM formulation can reduce agitation in 15 to 30 minutes
• Reduces positive symptoms; improves negative symptoms; aggression; affect; impulse control
• Helpful w/ bipolar mania

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Can improve psychotic and manic symptoms within 1 week; may take several weeks for full effect on affective symptoms

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Zyprexa (olanzapine)

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IM formulation can reduce agitation in 15 to 30 minutes

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Zyprexa (olanzapine)

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Reduces positive symptoms; improves negative symptoms; aggression; affect; impulse control

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Zyprexa (olanzapine)

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Helpful w/ bipolar mania

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Zyprexa (olanzapine)

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Zyprexa (olanzapine) Monitoring parameters:

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• Check fasting plasma glucose & lipids
• Check weight; overweight if BMI > 25.0-29.9; check every 3 months (should be done at every visit)
• Can put on weight REALLY fast.  useful as an initial go to when trying to stop a manic episode and then change to something else for maintenance.
• Take at bedtime to avoid daytime sedation
• Blocks H1 receptors ( sedation and weight gain)
• Blocks alpha 1adrenergic receptors ( dizziness, BP decrease)
• Blocks muscarinic receptors ( dry mouth, urinary retention, constipation)

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Check fasting plasma glucose & lipids

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Zyprexa (olanzapine)

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Check weight; overweight if BMI > 25.0-29.9; check every 3 months (should be done at every visit)
• Can put on weight REALLY fast.  useful as an initial go to when trying to stop a manic episode and then change to something else for maintenance.

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Zyprexa (olanzapine)

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Take at bedtime to avoid daytime sedation

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Zyprexa (olanzapine)

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Blocks H1 receptors ( sedation and weight gain)

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Zyprexa (olanzapine)

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Blocks alpha 1adrenergic receptors ( dizziness, BP decrease)

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Zyprexa (olanzapine)

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Blocks muscarinic receptors ( dry mouth, urinary retention, constipation)

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Zyprexa (olanzapine)

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Blocks H1 receptors ( sedation and weight gain)
• Blocks alpha 1adrenergic receptors ( dizziness, BP decrease)
• Blocks muscarinic receptors ( dry mouth, urinary retention, constipation)

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Zyprexa (olanzapine)

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TX of aggression/fighting/impulsivity

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Zyprexa (olanzapine)

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1st choice for a patient who is aggressive/explosive and needs to be stopped immediately!! (Depakote would also be a good choice and you are able to increase it FAST!) Risperdal is also a choice but it takes longer.

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Zyprexa (olanzapine)

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Risperdal (risperidone)

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• Can improve psychotic and manic symptoms within 1 week; may take several weeks for full effect on affective symptoms
• Reduction of aggression takes a bit longer
• IM injection every 2 weeks only for patients who show they can tolerate oral medication
• Reduces positive and negative symptoms; aggression; affect; behavioral disturbances
• High potency; has a long-acting depot (Consta)
• Used a lot in child (0.25 mg) and elderly (start with 0.5 mg) - document if used in an elderly pt w/ dementia- BBW
• Can start w/ 1 mg (range 1-6 mg- more is NOT better, will only increase EPS)
• Anna has only seen acute onset of dystonia with Risperdal

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If you miss doses on clozaril can u pick right back up on doses?

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no, you have to titrate back up again

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Can improve psychotic and manic symptoms within 1 week; may take several weeks for full effect on affective symptoms
• Reduction of aggression takes a bit longer

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Risperdal (risperidone)

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IM injection every 2 weeks only for patients who show they can tolerate oral medication

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Risperdal (risperidone)

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Reduces positive and negative symptoms; aggression; affect; behavioral disturbances

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Risperdal (risperidone)

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High potency; has a long-acting depot (Consta)

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Risperdal (risperidone)

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Used a lot in child (0.25 mg) and elderly (start with 0.5 mg) - document if used in an elderly pt w/ dementia- BBW

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Risperdal (risperidone)

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Can start w/ 1 mg (range 1-6 mg- more is NOT better, will only increase EPS)
• Anna has only seen acute onset of dystonia with Risperdal

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Risperdal (risperidone)

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Risperdal (risperidone) metabolized by

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2D6

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Co-administration of these can increase levels of Risperdal (risperidone)

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Paxil or Proxac

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pt comes in & he tells you he's aggressive and he will hurt someone and he's morbidly obese, what would you start him on?

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Depakote cuz increase it fast

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Risperdal (risperidone) Monitoring parameters:

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Metabolized by 2D6
• Co-administration of Paxil or Proxac may increase plasma levels of Risperdal
• Use with caution with cardiac impairment due to risk of orthostatic hypotension
• Controversial whether more or less risk for diabetes & dyslipidemia
• Only atypical that consistently increases prolactin
• Also comes in a dissolvable tablet
• Weight gain is not as intense as w/ Zyprexa

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Controversial whether more or less risk for diabetes & dyslipidemia

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Risperdal (risperidone)

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Only atypical that consistently increases prolactin

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Risperdal (risperidone)

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Also comes in a dissolvable tablet

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Risperdal (risperidone)

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Seroquel (quetiapine)

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• Efficacy-cognitive and affective symptoms
• Requires twice a day dosing; new XR QD
• May increase risk for diabetes and dyslipidemia
• Sedating at doses lower than 300mg QD- must cross this threshold in order for it to not be as sedating
• Stay at a dose < 300 mg to get a patient to sleep
• Give higher dose or single dose at QHS
• Minimal motor side effects (can increase prolactin levels)
• Blocks H1 receptors- Weight gain
• Blocks alpha 2 adrenergic receptors
• Blocks muscarinic 1 receptors
• XR product once a day dosing; dose 4 hours before bedtime to minimize daytime sedation (or for use as a hypnotic)
• Off label use as a hypnotic; side effect = restless leg syndrome

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Diff btwn depakote ER and reg depakote

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Reg take BID and ER take QD

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zyprexa + prozac=

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symbiax

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Geodon (ziprasidone)-

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$; onset of action slower (more useful for maintenance)
• FDA schizophrenia, bipolar, agitation, mania, psychotic depression
• Decreased weight gain and sedation
• Administration with food increases absorption two-fold
• Twice a day dosing with oral form (many do well with one dose at bedtime)
• IM form available-to initiate dosing or treat breakthrough agitation

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Geodon (ziprasidone)- Monitoring parameters:

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• Dosing too low can be activating
• Weight gain not expected
• Sedation usually at higher doses
• Monitor weight, blood pressure, and fasting glucose and lipids within 3 months and then annually

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Abilify (aripiprazole)

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• Dopamine partial agonist-3rd generation
• Works to reduce DA and to increase DA
• Can cause akathisia and/or activation
• Weight gain and sedation are unusual
• Once a day dosing 15-30mg daily
• Long half life-75 hours  consider this w/ cross titration (longer washout period)
• EX: Anna's female pt w/ BPD who got mouth twitching @ 25 mg (30 mg is max dose)
• Not at all sedating  sleep can be an issue. Use Trazadone for a hypnotic.

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Check wt at every visit with this med?

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zyprexa

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IM name of Risperdal?

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Consta

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Newer medications

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• Saphris - asenapine
• Fanapt - iloperidone
• Latuda - lurasidone
• Invega – paliperidone

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Cross titration exercise: Anna's patient ex: on Abilify 20 mg (maintenance dose), and then developed the mouth twitch and so changed to Geodon 40 mg BID
Literature says

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that you can start 2nd antipsychotic at the maintenance dose of the 1st antipsychotic  ok to just add Geodon
Safe: dropped to Abilify 10 mg and the added Geodon 40 mg

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Seroquel 300 mg BID. Drop the AM dose and change it to 300 mg q HS & add ability 15 mg x 1 week. Then totally stop Seroquel after

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1 week, only on Abilify now.

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Rule: Want to always have the antipsychotic in their system (can never totally stop the 1st antipsychotic = s/s return

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). Safe to add 2nd product as long as it is not for a prolonged period of time (5 days-1 week)

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Extrapyramidal Symptoms (EPS) Definition:

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Involuntary motor abnormalities related to a dysfunction of the EP system

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EPS Typically occurs

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in 1st 90 days of treatment

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3 categories for EPS:

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acute dystonias; akathisia; parkinsonian syndrome

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Must be assessed with AIMS

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when on antipsychotics

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EPS precedes

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TD

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Acute dystonia

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Anna has seen w/ Risperdal. Extreme body twisting
• Slow-sustained muscular contraction; involuntary
– Neck (torticollis)
– Jaw: forced opening, dislocation
– Tongue protrusion; twisting
– Body-twisting movement
– Laryngeal: can constrict airway
– Occurs in 10% of patients; > in young males
– Usually at start of treatment; can occur later

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Treatment of Acute dystonia

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• **Considered a medical emergency**
• Outpatients should be instructed to go ER
• Rule/out seizure disorder
• IM injection can treat within minutes
• First line treatment
– Benztropine- Cogentin IM
– Diphenhydramine- Benadryl
– Second-line-benzodiazepines

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Parkinsonian Syndrome

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• Affects 15% of patients
• **Symptoms:
– Muscle stiffness
– Lead-pipe rigidity
– Shuffling gait
– Stooped posture
– Drooling
– Pill rolling tremor
– Coarse tremor
– Bradykinesia
– Rabbit syndrome: perioral tremor; late in treatment

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Treatment of Parkinsonian Syndrome

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• Prophylactic use of anti-parkinsonian agent is less common with newer generation of antipsychotics
• Treat with anticholinergic agents for 6 weeks (is stopping TX, but if not, add on for the duration of TX)
– Cogentin (benztropine) orally (1 mg daily)
– Artane (trihexyphenidyl)
– Benadryl (dephenhydramine)
– Amantadine (symmetrel)- DO NOT GIVE IF PSYCHOTIC S/S PRESENT

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Akathisia- looks VERY similar to anxiety

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• Feelings of discomfort, agitation, restlessness
• May pace relentlessly, alternating between standing and sitting
• Can occur anytime during treatment
• Often missed; perceived as anxiety

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Treatment of akathisia

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• Lower antipsychotic dose (if at a high dose)
• Change to a different medication
• First-line agents: beta-blockers:
– Beta blockers-Propanolol, atenolol; anticholinergics- Cogentin
• Second-line agents:
– Amantadine (Symmetrel)
– Benzodiazepine- long acting (Lorazepam- use if a lot of other meds are on board, Clonazepam)

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Tardive Dyskinesia

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chronic blockade of DA receptors; irreversible
• Definition: Persistent, abnormal involuntary muscle movements
• EPS is a pre-cursor
• Can be irreversible
• May include head, limbs, and trunk

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**Symptoms of TD

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• Presentations:
– Perioral movements: darting, twisting & protruding of tongue; chewing and jaw movements, lip puckering (most common)
– Facial grimacing
– Finger movements, hand clenching
– Torticollis-trunk twisting and pelvic thrusting (severe cases)

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Treatment of TD • PREVENTION:

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– Use lowest possible doses of medications
– Use newer generating medications
– Regular assessment with AIMS

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• TREATMENT of TD

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– Can decrease or discontinue antipsychotic medication (possibility S/S will worsen)
– Use of mood stabilizing agents, benzos
– Last resort: 3rd line: change to Clozaril/clozapine

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Neuroleptic malignant syndrome

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more common in young males; high mortality rate

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Neuroleptic malignant syndrome

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• Life threatening syndrome of unknown pathophysiology with behavioral, muscular changes and autonomic arousal
• Often missed in early stages
• More common in male, young patients
• Lasts 24-72 hours; untreated 10-14 days has a 20-30% mortality rate
• Mortality rates are higher with Depot use
• S/S: high fever, seizures, eventually coma & death

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Class warning

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Hyperglycemia and Diabetes Mellitus

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Class warning: Hyperglycemia and Diabetes Mellitus
• Symptoms are:

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– Polyuria, polydypsia; blurred vision, tingling or numbness in extremities, recurrent infections, dry, itchy skin, slow to heal from bruises or cuts

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Class warning: Hyperglycemia and Diabetes Mellitus get these levels

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Fasting Plasma Glucose (FPG)
• <110mg/dl = normal fasting glucose
• >110 and < 126 = impaired fasting glucose
• >126 = diabetes

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Treatment Guidelines for Schizophrenia

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• Most respond within 1 to 2 months
• Typical response: 30-40% reduction in symptoms

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Treatment Guidelines for Schizophrenia • Required monitoring:

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– AIMS test (abnormal involuntary movement scale)- check for tongue protrusion, grimacing, extend hands and check for tremor, let arm go limp and place hand at base of arm and have them make a fist upward and of there is EPS there will be a cogwheel rigidity, neck jerking against resistance
(-) AIMS if nothing is found
– CBC – clozapine
– Cardiac QT prolongation- problem w/ Seroquel
– Weight, lipids, blood glucose

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Morbidity and Mortality of schizo

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• Life expectancy 20% shorter than general population
• Morbidity
– Poverty, limited insight & lack of access to care
• Mortality
– Increased natural and unnatural causes of death
– 10% commit suicide

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Weight management of schizo

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• Make weight a routine part of evaluation
• Educate about weight issues prior to starting medication
• Weight is difficult to lose even with diet and exercise
• Consider switching medication after risk/benefit assessment

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**Cardio-metabolic risk
• Four parameters to monitor:
in shizo

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– Weight and body mass index (waist circumference)
– Fasting triglycerides
– Fasting glucose
– Blood pressure

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Monitoring parameters of schizo

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• Vital signs – blood pressure
• Fasting lipid profile and blood glucose prior to treatment, in 3 months, annually
• BMI, personal/family history of obesity
• Waist circumference
• Mental status exam
• AIMS scale – EPS
• Weight at baseline, at 4, 8, 12 weeks and then quarterly. Consider changing meds if weight gain > 5% of the initial weight