Chapter 13: Psychotherapeutic Medications

Psychotherapeutic Medications definition

* exert a special or unique effect on the mind or mental functioning

Non-pharmacological treatments in history

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* cruel ways people were treated for their mental illnesses before psychotherapeutic medications
* cleansing an individual who has the mental illness

examples of non-pharmacological treatments

* bloodletting
* hot irons
* flogging
* revolving chairs
* starvation
* sneezing powder
* sneeze away the mental illness

Non-pharmacological treatment when mental illness progresses

* they would be isolated from society so that they wouldn’t cause harm
* be left alone
* still around with psych wards

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Lobotomy

* a spike is hammered through the skull and damages some part of the brain
* damaging the brain to get rid of the disorder
* changing people’s behaviors by causing damage to the brain
* loss of brain matter

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What part of the brain does a lobotomy target

* prefrontal cortex

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Howard Dully

* had childhood schizophrenia
* parents and doctors wondered what was going on and what can be changed to make him ‘normal’
* face was swollen after the lobotomy procedure
* first to have the lobotomy procedure done to him

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First revolution in medicine

* the discovery of vaccines in the 19th century
* louis Pasteur

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Louis Pasteur

* pasteurization/rabies
* vaccine/germ theory

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Second Revolution of medicine

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* WWII antibiotics
* using antibiotics to treat diseases
* Selmon Waksman

Selmon Waksman

* streptomycin
* neomycin

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Third Revolution in pharmacology

* psychopharmacology
* chlorpromazine era
* Paul Charpentier

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Chlorpromazine era

* initially for anesthesia
* decreased surgical anxiety and shock after surgery
* used to calm psychotic patients
* spread worldwide and the number of psychiatric patients dropped

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Val-de-grace military hospital

* used chlorpromazine to calm psychotic patients
* their thoughts became less chaotic
* no loss of consciousness

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Emil Kraepelin, Philip Pinel, JE Esquirol

* pioneers in developing a mental illness classification system
* believed we needed scientific understanding before a treatment was given

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involvement in cannabis in treating mental illness

* Moreau’s use for treating depression and manic patients
* temporary effects while individual was intoxicated
* replaced disorders negative symptoms with good effects of drugs

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Pre 3rd revolution solutions to mental illnesses

* Amphetamines for narcolepsy (kept people up)
* CO2 for psychosis and neurosis (using gas to treat people)
* Antihistamines, insulin shock (psychosurgery: surgically disconnecting brain structures)
* Electroshock Therapy (last resort)
* Lithium used for mania
* Antipsychotic Medications

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Lithium treatment (what was it used for) (why was it not approved)

* used for mania
* john cade 1940s
* not approved in the US until 1970 because of toxicity concerns
* still used today for bipolar disorder

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Phenothaizines

* neuroleptic medication (neural depressants) or major tranquilizers
* first gen antipsychotics

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Psychosis

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* loss of contact with reality
* naturally occurring, not drug-induced
* disorganized thinking and bizarre behavior

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Post Chlorpromazine Era (what medicine) (advances in what)

* Reserpine
* Advances in:
* anti-anxiety
* antidepressants
* ketamine

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Reserpine

* originally intended for arterial hypertension
* side-effect - symptoms of indifference
* took several weeks for effectiveness to kick in
* patients often depressed so it ultimately never took off

use of LSD as a model psychosis

* used to better understand mental illness
* limited success

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National Comorbidity Survey Replication (NCR-S) - 2005

* 9,000 adult household survey
* focused on anxiety (panic, PTSD), mood (depression, bipolar), impulse control (ADHD), substance abuse

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Findings of NCR-S (testing disorders in adults)

(when do symptoms appear, how many us adults meet the criteria for mental illness)

* 1 in 4 US Adults yearly
* of which 1 in 4 had serious disorder (affecting day-to-day)
* anxiety (18%)
* mood 10%
* impulse 9%
* substance 15%
* \~50% US Adults meet the criteria for mental illness at some point in their lives
* comorbidity in about half
* most don’t get treatment
* symptoms appear early
* 1/2 byt 14 years

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mistakes of the NCR-S

* didn’t include homeless, institutionalized, or prisoners
* didn’t assess less common psychiatric disorders like schizophrenia and autism

NIMH mental illness Findings 2021

* about 23% of US adult population has some kind of mental illness
* separated by sex, age, race
* less than 50% have received treatment

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Serious mental illness NIMH 2021 findings

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* about 5% have serious mental illness and about 65% of them have received treatment

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Serious Mental illness definition (NIMH)

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* mental, behavioral, or emotional disorder resulting in serious functional impairment, interfering with or limiting major life activities

Hospital visits for mental disorder trends

* rates go up each year but then stabilized over the last 15-20 years

trend among users of psychotherapeutics

* 2 timers higher in women than in men
* symptoms of men’s mental illnesses was more socially expectable than women symptoms
* men can have high egos where they don’t need it
* uses increases with age
* most dramatic in men
* higher individuals
* living alone
* with more education
* with more income

Problems with psychotherapeutic medication (criminal, medical, misuse)

* criminal
* people still will traffic these drugs because you can get them on the street cheaper than at pharmacies
* medical
* not finding the right kind of treatment
* misuse
* benzos

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Rates of prescriptions of psychotherapeutic in the past few years

* increased
* not all went up but antidepressants did

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Famous patients with schizophrenia

* John Nash
* Elyn Saks

John Nash

* won nobel prize in economic sciences
* a beautiful mind movie about his story

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Elyn saks

* big voice in schizophrenia community
* overcame and controlled her schizophrenia
* professor of law, psychology, and behavioral sciences

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Famous patients with major depressive disorder

* jim carrey
* dwayne johnson

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Famous patients with bipolar disorder

* demi lovato
* mariah carey

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Schizophrenia produces disturbances in what areas

* language
* affect
* perception of reality
* changes in behavior

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percent of population with schizophrenia and trend based on sex

* \~1% of population
* higher in men
* can be because women may exhibit symptoms differently

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Schizoaffective Disorder

* previous or concurrent depressive/manic episode
* variety of symptoms with more on the emotional side

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Paranoid Schizophrenia

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* delusions and/or auditory hallucinations
* visual disturbances are not that common and it is more auditory disturbances

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what symptoms do antipsychotics treat

* agitation
* mania
* hallucinations
* delusions
* anger
* accelerated/disorganized thinking processes

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Dopamine Hypothesis - schizophrenia

* dopamine system may be disturbed in those with schizophrenia
* originates from amphetamine-induced psychosis as model

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by blocking the reuptake of dopamine, what happens…

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what do antipsychotics block and what does this do?

* mediated by increases in dopaminergic activity
* by blocking the reuptake of dopamine, levels of dopamine is elevated and we induce a psychosis-like behavior
* antipsychotics ‘block’ postsynaptic DA receptors
* D2 receptors that block dopamine receptors can alleviate the drug induced psychosis

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First Generation of Antipsychotics drugs (what receptors does it effect)

* phenothiazines
* antagonists of dopamine receptors
* blocked dopamine receptors leading to a decrease in psychosis symptoms
* Target Nigro-Striatal Pathway
* blocks acetylcholine receptors

how do first gen antipsychotics target the dopamine system (where does it target D2 receptors and what does it activate)

* mainly target D2 receptors in the reticular activating system which works on keeping you conscious and controls your behavioral arousal
* affects D2 in limbic system and hypothalums

D2 found in limbic system controls

* emotional arousal

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D2 found in hypothalamus controls

* metabolism and alertness

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problems with first gen antipsychotics

* effects motor control
* Dyskinesia
* Akinesia
* affects cholinergic system involved in neuromuscular junction

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Tardive Dyskinesia (disordered)

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* effects \~1/3 of patients who have long term use of first gen antipsychotics
* causes
* tremors
* face twitching
* involuntary movements
* becomes exhausting from your body constantly moving and unable to relax

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Akinesia

* slowing down of motor control

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How is the nigro-striatal pathway affected by first gen antipsychotics

* it is the pathway for planning and modulation of movement and D2 receptors are found here which are the receptors that first gen antipsychotics target, leading to effect in movement

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Neuromuscular junction effects of first gen antipsychotics

* dry mouth
* dry eyes
* constipation
* sexual dysfunction

2nd generation antipsychotics (atypical) - 1990s examples

* non-phenothiazines
* clozapine
* risperidone

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Advantages of 2nd gen antipsychotics (actual, not increase quality of life)

* reduce receptor blockade in nigro-striatal pathway
* reducing motor impact
* greater impact on serotonin system
* better chances alleviating symptoms without negative side effects

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Side effects to 2nd gen antipsychotics

* weight gain
* Agranulocytosis
* fatal myocarditis

Agranulocytosis

* bone marrow doesn’t produce white blood cells

Fatal Myocarditis

* inflammation of the heart lining

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which generation of antipsychotics has a better quality of life

* 2nd gen

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Aripiprazole (Abilify) (D2 is antagonist and agonist in what state)

* technically like 3rd generation
* stabilizes DA
* Targets the DA D2 receptors
* D2 receptor antagonist in hyperdopminergic state
* D2 receptor agonist in hypodopaminergic state
* Doesn’t block it like others, instead it changes the general levels of dopamine

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Other neurotransmitters involved in schizophrenia other than dopamine and why (3)

* glutamate system
* ketamine can block glutamate receptors and can produce perception of reality
* became a new option for a variety of disorders
* GABA System
* if there is too much dopamin, targeting GABA that effects dopamine can help
* cannabinoid system

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What else can antipsychotics treat

* mania
* agitated depression
* drug-induced psychoses
* emotionally unstable personalities
* psychoses with old age
* natural-aging processes
* dementia

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how much of the US population has a lifetime diagnoses of major depression

* \~20%

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combination of what two things can be the cause of depression

* genetic and environmental features

Depression is thought to be due to what (decrease in what)

* decrease in catecholamines

Catecholamine hypothesis

* due to effects of reserpine (people became indifferent and depressed)
* we originally thought it was norepinephrine
* we thought it was for norepinephrine system due to observations of reserpine effects
* amygdala and reticular formations
* big culprits in the symptoms

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serotonin hypothesis for depression

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* reduced serotonin and increase in enzymes in cerebrospinal fluids that decrease serotonin levels
* Effects brain stem
* serotonin system orignates in the brain stem

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MAOIs

(what is it and how does it)

* monaine oxidase inhibitors
* class of anti depressants in the 1950s
* breaks down monamines so that neurotransmision is terminated

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MAOIs examples My NP

* Nardil (phenylzine)
* parnate (tranyl cypromine)

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MAOIs mechanism of action (what does it inhibit)

* percent breakdown of monamines leading to monamines in the synapse longer
* inhibit enzymes that breakdown monamines leading to monanines in the synapse longer

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side effects of MAOIs

* temporary low BP
* impaired sexual performance
* dietary restrictions
* Monamines break down tyramine so taking MAOIs disturbed that process
* can’t have tyramine which was in cheese

Tricyclics examples Try ET

* Elavil (amitriptyline), Tofranil (Imipramine)

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Tricyclics mechanism of action (cyclics) (interfere with what causing what) (primarily targets what) (block what)

* interfere with monamine system but primarily target serotnin, norepinephrine, noreadrenaline by blocking the transporters that take up these monamines from the synapse
* they hang out in the synaptic cleft longer because they aren’t sucked up
* similar to stimulants but without addiction liability
* Blocks various postsynaptic receptors
* histamine
* muscarinic acetylcholine receptors
* combination of blocking all of it can alleviate symptoms of depression

side effects of tricyclics

* Drowsiness 


* Anticholinergic effects 
* Dry mouth 
* Constipation 
* Difficulty urinating 
* Blurred vision 
* Dizziness upon standing 
* Decreased libido 
* Weight gain 
* Tachycardia
* risk for fractures

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Heterocyclics (what is it? what is it more effective compared to)

* SSRIs - serotonin selective reuptake inhibitors
* more effective than tricyclics because it is more selective
* fewer side effects
* not everyone benefits and there are unwanted side effects so atypical agents were made

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Example of heterocyclics (also SSRIs)

Fluoxetine (Prozac); Paroxetine (Paxil); Fluvoxaine (Luvox); Sertraline (Zoloft)

Heterocyclics mechanism of action

* mainly effecting the serotonin system because they are selective for it
* SSRI’s block the serotonin transporter leading to the serotonin hanging out in the synapse longer activating the serotonin receptors more

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Atypical agents examples

* effexor
* cymbalta

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Atypical Agents (what does it effect)

* can effect norepinephrine more or some dopamine and some serotonin
* combination of effects
* better outcomes in individuals who have depression

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SNRI’s

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* serotonin and norepinephrine
* Wellbutrin (Buproprion, Zyban)
* Weak DNRI -> Dopamine, norepinephrine 
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Caveat of taking antidepressants

* whether atypical or SSRI, abrupt cessation should be avoided
* stopped taking the medication all of a sudden can cause suicidal thoughts and sinfidicant anxiety as well as other symptoms

Paradox with antidepressants

* antidepressants have paradoxical effects
* can increase depressive thoughts and symptoms
* can numb all emotion rather than just the sads ones
* relief isn’t felt right away

how long do the behavioral effects of antidepressants take and why is it an unusual amount of time

* takes 2-10 weeks
* molecular actions are immediate (elevated monamine levels)

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Neurogenesis

* stimulating new generations of neurons and stimulating the mechanism

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how long does neurogenesis take

* slow process
* \~2-3 weeks

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what factors are critical for stimulating neurogenesis

* neurotrophic factors
* brain-derived neurotrophic factors (BDNF)

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what class of drugs increase neurogenesis

* antidepressants

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how can we help the speed of antidepressant effects (what can we do to get those effects faster)

* coming up with drugs that stimulate the process of neurogenesis quicker may be more effective and help effects come quicker

Neurotrophic hypothesis of depression (neurotransmitters and BDNF levels after taking antidepressants)

* people take the antidepressants and within hours there are some elevation of neurotransmitters that creates signaling cascades of a variety of neurons. Eventually one of the cascades of event can trigger the transcription of specific genes in DNA including neurotrophic factors (BDNF) leading to increased levels of BDNF in cells and nervous system
* presence of BDNF triggers neurogenesis and existing neurons will grow new synapses dendrites, connections, etc

differences in brains between people with and without depression

* people with depression may not have the right number of connections in the brain and may have less potential connection points

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according to the neurotrophic hypothesis, what can be the treatment for depression

* more synaptic connections

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how do antidepressants help synaptic connections (what does it stimulate and what does that do)

* they stimulate the rise of monoamines allowing the cascade of events to happen eventually leading to an increase in synaptic connections

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what happens to a person if they get off their antidepressants

* if people get off of the medication, their system may revert to the old form because that’s how their body naturally is

short term effects of antidepressants

* increase in serotonin and norepinephrine

long term effects of antidepressants and how long it takes

* 3-8 weeks
* greater BDNF levels, more synaptic proteins, more neurons and dendritic sprouts leading to a decrease in depression

what receptor is ketamine an antagonist for

* NDMA Antagonist (glutamate)

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What psychotherapeutic drug can ketamine work as

* a faster working antidepressant

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Ketamine Animal Experiment

* noticed the control brain had few dendrite spines while the ketamine brain had more dendrite spines showing more potential for synaptic connections
* part of neurogenesis is the creation of new connections/synapses
* potential for new synapses and connections to be formed in rodents

Dendrite Spines

* where synapses form