Mon 11/9 Depression, Bipolar etc Flashcards
Short definition of depression
intense feelings of sadness and despair
True or false: depression is the more prevalent mental illness.
TRUE - 15-20% of adults experience a major depression at some point in their lives
True or false: Men are more likely than women to develop depression
FALSE - Women 2X as likely as men
True or false: Depression affects only the elderly
FALSE: Becoming more commonly diagnosed in younger age groups
6 Characteristic signs of depression
Sleep disorders Somatic complaints Anorexia Irrational guilt General lack of interest in activities Dysphoric mood
2 good screening questions for depression
“Over the past 2 weeks have you felt
(1) down, depressed, or hopeless, and/or
(2) little interest or pleasure in doing things?”
3 Possible interacting factors that cause depression
Interaction of biochemical , environmental & genetic factors
How does a person become depressed? (4 possible explanations)
- Decreased activity of the postsynaptic receptor
- Decreased activity of BDNF
- Decreased capacity for neurogenesis caused by high glucocorticoid levels
- Supersensitivity of the presynaptic autoreceptor
What are the three amines involved in development of depression and what is their main role?
Amines: - Serotonine, - Dopamine , - Nonepinephrine Found all over the brain – control movement and activity
Explain the supersensitivity of the presynaptic autoreceptor:
Autoreceptors found in the presynaptic side – in the button senses the amount of neurotransmitter in the synaptic cleft and modulate secretion at the presynaptic side
If the receptor is supersensitive it is going to think there is too much serotonin in the cleft so it will dial down secretion.
Name the 3 pharmacological targets for depression
- Inhibit breakdown of neurotransmitters
- Stimulate release of neurotransmitter
- Block reuptake of neurotransmitter
What’s the overall goal in treatment of depression, bipolar disorders and schizophrenia?
Increase aminergic neurotransmitters which increase synthesis of BDNF
Name a few activities that increase BDNF activity
Exercise,
Continue learning
Solve cross-word puzzles
Use your brain
What is the precursor chain for serotonin and nor-epinephrine?
Two separate pathways:
Tyrosine -> Dopamine->nor-epinepherine
5-hydroxytryptophan ->serotonin - >melatonin
What is serotonin a precursor for?
Serotonin -> melatonin (depletion could result in sleep disorders; one of the reasons why depression, bi-polar disorder and schizophrenia are associated with sleep disorders;
How could you describe Bipolar Disorder?
Take all the things that go wrong with depression, and add a GABA imbalance.
Mechanisms are not clear.
GABA – is the inhibitor; it could be a GABA inbalance which adds to the impulsivity and the maniac behavior
How does someone become psychotic? (3 possible mechanisms)
- Hyperactivity of dopamine
- Insufficiency of GABA at modulating glutamatergic activity in the limbic system
- Overlap of the activity of DA, serotonin, GABA, glutamate, and nor-epinephrine make the parthenogenesis difficult to elucidate.
True or false: the cause of psychotic behavior is purely genetic
False: it is a combination of genetic inheritance and environmental factors
What would be a possible treatment for psychosis?
Dopamine receptor blockers is the treatment, but be cautious of Parkinson’s like syndrome when prescribed as well as the other disorders that could be caused by blocking dopamine receptors.
What is the recommendation when administering psychotropic drugs?
When starting, drug may be “laddered in” gradually to therapeutic level – may take 2-4 weeks for therapeutic threshold to be reached
What are some activities that PT could recommend while waiting to reach desired therapeutic effect with psychotropic drugs?
- Remind your patients not to get discouraged; also may see increased depression during this time
- Exercise and therapeutic activities can be very beneficial
Will PT sessions be affected by timing of the psychotropic drugs or other factors during drug therapy?
Timing therapy – should not matter when patient at therapeutic level, but monitor for orthostatic hypotension for tricyclics and lithium, especially in early stages, and especially in elderly patients
How would you educate a patient to manage the process of discontinuing a psychotropic drug?
Patient should NEVER abruptly stop taking psychotropic drugs
- Just like cortisone or seizure medications, the body acclimates to these drugs and alters biochemistry accordingly;
- Abrupt withdrawal is dangerous and cause disruption of all systems affected by the respective neurotransmitters;
What are the 5 functional categories of antidepressant drugs?
- Selective Serotonin Reuptake Inhibitors (SSRI)
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
- Tricyclics
- Monoamine Oxidase (MAO) Inhibitors
- Other compounds
Name 6 common SSRIs
Celexa Lexapro Prozac Luvox Paxil Zoloft
Name 3 common SNRIs
Pristiq
Cymbolta
Effexor
Name a few tricyclics:
Elavis, Endep Asendin Anafranil Norpramin Sinequan Norfranil, Tofranil, others Aventyl, Pamelor Vivactil Surmontil
Name 3 MAO inhibitors:
Nardil
Marplan
Parnate
Name 4 drugs listed under “other” antidepressants
Wellbutin
Desyrel
Remeron
Serzone
What is the mechanism of action for SSRIs?
Serotonin helps regulate mood and depression.
By blocking reuptake into the presynaptic terminal, serotonin remains in the synaptic cleft longer, hopefully contributing to beneficial change in receptor sensitivity or neuronal growth and function
For patients whose primary issue is serotonin depletion, these are great drugs
What are the few side effects associated with SSRIs?
may cause sexual dysfunction, anxiety, nausea, insomnia, long half-life can lead to accumulation
What is Paroxetine (Paxil) also used for (other than depression and bi-polar disease ?
Chronic pain
What is the mechanism of action for SNRIs?
Decreases both serotonin and norepinephrine reuptake without appreciable effect on dopamine synapses
Have the same safety and antidepressant effects comparable to SSRIs and tricyclics
What are SNRIs also used for (other than depression and bi-polar disease?
Chronic pain:
Osteoarthritis,
Peripheral neuropathies,
Fibromyalgia)
What is the believed reasoning behind serotonin being useful in pain control?
Postulated that ↓ serotonin in efferent (descending) pathways that inhibit pain are a cause of chronic pain; restoring serotonin influence therefore improves pain control
What are the side effects associated with SNRIs?
Same as SSRIs side effects + GI distress
Explain Serotonin Syndrome
- Serotonin syndrome can be fatal
- High doses, or 2 or more antidepressants administered concurrently
- Serotonin accumulates in brain tissues – if levels become too high, will see sweating, restlessness, agitation, tachycardia, neuromuscular hyper excitability (tremor, clonus, fasciculation, rigidity)
- Danger of seizures, fatality
- Reversible if drugs withdrawn
What is the mechanism of action for MAO inhibitors?
Monoamine oxidase is an enzyme located at the enzyme synapses,
It destroys released transmitters
Inhibiting MAO allows more of the transmitter to stay in the synaptic cleft
Can have beneficial effect on receptor sensitivity and neuronal function
What are the side effects associated with MAO inhibitors?
relatively high risk of side effects:
- CNS excitation, agitation, irritability, sleeplessness
- Produce central and peripheral anticholinergic effects (tremor, dry mouth, urinary retention)
- ↑ BP
Name a few of the MAO inhibitors interactions
it is a long list from drugs. com mainly
- Interactions between MAO type A inhibitors and foods such as fermented cheeses and wine (any food containing tyramine) - ↑catecholamines, which can cause heart attack or stroke
-diet pills, caffeine, stimulants, ADHD medication, asthma medication, over-the-counter cough and cold or allergy medicines;
tryptophan (also called L-tryptophan);
levodopa (Larodopa, Parcopa, Sinemet), methyldopa (Aldomet);
meperidine (Demerol, Mepergan);
furazolidone (Furoxone);
procarbazine (Matulane);
buspirone (BuSpar);
bupropion (Wellbutrin, Zyban);
dexfenfluramine (Redux);
guanethidine (Ismelin); - alcohol or medicines that make you sleepy (such as cold medicine, pain medication, muscle relaxers, and medicine for seizures, depression or anxiety);
or - antidepressants such as citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), or venlafaxine (Effexor).
What is the mechanism of action for tryciclics?
- Block reuptake of amine neurotransmitters into presynaptic terminal
- Non-selective, so block serotonin, norepinephrine, dopamine
What is the target population for Tryciclics?
Now mostly reserved for patients who fail with SSRIs or SNRIs
What are the side effects associated with Tryciclics?
- Sedating, lethargy, muscle weakness
- Confusion and delirium, as central acetylcholine is blocked
- Peripheral anticholinergic effects – dry mouth, constipation, urinary retention, confusion, tachycardia
- Arrhythmias, orthostatic hypotension, bone marrow depression
- Highest potential for lethal overdose due to cardiac effects
- Increased suicide risk
- High potential for drug interactions, especially cardiovascular and other neurotropics
True or False: most of the antidepressants used to treat chronic pain are tryciclics
True - All but 3 (Cymbalta - SSRI, Prozac - SSRI, and Desyrel) are tricyclics
Could you say with certainty that the swap from narcotics to tryciclics is a good choice considering all the side effects?
Not necessarily the best choice
Should be reserved for those who have failed conservative treatment
Monitor for side effects
Mechanism of action still under investigation
Define Bi-Polar Disorder:
Mood swings between extreme high (manic) and low (depression)
What are the behaviors characteristic to a maniac episode?
Hyperactivity, extremely talkative, may exhibit extreme confidence or anxiety
Differentiate between Bipolar I and Bipolar II
Bipolar I - alternating mania and major depression
Bipolar II – hypomanic episodes, still has major depression
What are the most likely the neurotransmitters involved in Bipolar disorders?
- Most likely an imbalance between inhibitory transmitters (serotonin, GABA) and excitatory (norepinephrine, dopamine, glutamate, aspartate)
- Other neurotransmitters (acetylcholine), hormones, membrane ions, dysfunction of messenger systems may be involved
What is the drug of choice for Bipolar Disorders?
Lithium has been drug of choice for >60 years
Why is Li+ the drug of choice for Bipolar Disorders?
- May compete with Na+, K+, Ca++
- Multiple possible pathways of interaction
- May prevent neuronal degeneration and sustain function
- May be neuroprotective
Li+ administered orally, easily absorbed in GI tract; titrated to achieve desired blood serum level
What are the Lithium adverse effects?
- May accumulate in the body; is not metabolized and must be excreted in urine; if accumulated, may cause seizures, coma, fatality
- Sedation, muscle weakness, and lethargy, similar to tricyclics
- Mild to severe Li+ toxicity in CNS, GI, cardiovascular, renal systems.
What are some secondary drugs for Bipolar Disorders?
- Anti-seizure meds and
- Antipsychotics (Risperdal [risperidone], Abilify [aripiprazole], Clozaril [clozapine])
What is the effect of secondary drugs in Bipolar Disorders?
Secondary drugs act as mood stabilizers
- may be withdrawn when behavior levels out
Define the term Psychosis
Generic term for a group of mental disorders characterized by thought disturbances and impaired perception of reality
What is the most common Psychotic disorder? what about others?
Schizophrenia
Psychosis includes schizoaffective, delusional, brief psychotic, and shared psychotic disorders
Are psychosis curable and what’s the role of medication in Psychosis treatment?
Not thought to be curable; goal of medications is to normalize behavior and thinking sufficiently to allow a positive and potentially productive life in the community
Is Schizophrenia genetic or not and when does it manifest?
Likely has a genetic base, or modifications of gene expression (epigenetic factors) during life
– illness may not be seen until some stressor (physical, environmental, mental, chemical) brings it out
What is the neurotransmitter responsible in schizophrenia? and what type of drugs are administered?
Over activity of dopamine pathways
First generation or “traditional” antipsychotics – dopamine antagonists
What are the specific behaviors of schizophrenia?
Hallucinations,
Delusions,
Disorganized speech,
Grossly disorganized or catatonic behavior
What are the side effects of the Atypical Antipsychotics?
Fewer side effects, especially movement and motor disorders: tardive dyskinesia, pseudoparkinsonism, akathisia, Dyskinesia and Dystonias
May also have lower incidence of relapse
What are the possible side effects for all antipsychotics, particularly for the traditional ones?
- Sedating
- Orthostatic hypotension during first stages of new drug -administration
- Extrapyramidal effects (tremor, slurred speech, akathisia (constant motion), dystonia, anxiety, distress, paranoia, sluggish thinking)
- Anticholinergic effects (constipation, dry mouth, blurred vision, dizziness, urinary retention)
- Tardive dyskinesia – involuntary and fragmented movements, such as tongue and orofacial movements, extremity/trunk dystonias – may be irreversible
- Pseudoparkinsonism (due to blocking of dopamine)
- Neuroleptic malignant syndrome (seen in high dose medications) – catatonia, stupor, rigidity, tremors, fever – may be fatal
What are 3 possible side effects for all antipsychotics, particularly atypicals (highest risk with Clorazil and Zyprexa)?
Weight gain, increased plasma lipids, diabetes mellitus
