Drug for Depression & Anxiety Flashcards
Locations of the neuron circuitry regulating anxiety and fear
subcortical (subconscious)
Fear
an emotional state aroused by specific external stimuli that gives rise to defensive and escape behaviours
Anxiety
a generalized response to an unknown threat or internal conflict. Some argue that anxiety occurs when a person recognizes that they are not in control of the outcome of a threatening situation
bilateral degeneration of amygdala
patient lives without fear
Anxiety Disorders
psychiatric conditions characterized by overactivity of the autonomic nervous system, expectation of an impending threat and continuous vigilance of danger (not caused by drug intoxication or withdrawal)
Panic disorder
Episodic periods of intense fear and ANS over activation (fast heartbeat, short breath & patients sincerely think they are dying)
Generalized anxiety disorder
Persistent state of excessive worry and anxiety serious enough to cause a disruption in normal activities
Anticipatory anxiety
A fear of having a panic attack; may lead to agoraphobia
Agoraphobia
A fear of being away from home or another protected place
Social anxiety disorder
Excessive fear of being exposed to the scrutiny of other people that lead to avoidance of social situations
Post-traumatic stress disorder
A reaction to a terrifying event that occurs to or is witnessed by the patient. Characterized by flashbacks, nightmares, anxiety and compulsive thoughts about event
lifetime prevalence of anxiety disorders
20 % (most prevalent psychiatric condition)
Biological causes of anxiety disorders
- Females 2x as likely as males to develop an anxiety disorder.
- but heritability is low compared to other psychiatric conditions (0.3).
- major factors are environmental & not genetic
Brain regions important in Anxiety
- Amygdala
- Hypothalamus
- Anterior pituitary
- Adrenal gland
Cortisol (stress)
causes immune suppression, weight gain & causes some of synapse connections to detach & disappear (especially in hippocampus)
adrenal gland
produces adrenaline & cortisol
First-line pharmacotherapy for anxiety disorders
SSRIs (selective serotonin reuptake inhibitors)
fMRI
functional magnetic resonance imaging
*used to measure changes in blood flow - more neuron activity = more blood
the brain of patients with anxiety disorders show…
an over activation of the amygdala
DTI
diffusion-tensor imaging
GAD and PD can also be treated with…
Benzodiazepines (at low dose)
but have limitations due to tolerance, withdrawal, rebound effect, abuse liability
Disability is measured in:
DALY = How many years of healthy life are lost to the disease
Major Depressive Disorder (MDD)
- Depressed mood most of the day.
- Diminished interest or pleasure in all or
most activities. - Significant unintentional weight loss or
gain. - Insomnia or sleeping too much.
- Agitation or psychomotor retardation
noticed by others. - Fatigue or loss of energy.
- Feelings of worthlessness or excessive
guilt. - Diminished ability to think or concentrate,
or indecisiveness.- Recurrent thoughts of death.
- Diminished interest or pleasure in all or
MRI
used to measure brain volumes and detect lesions and malignancies Volume loss thought to reflect loss of synapses or less neurogenesis in MDD
Heritability of Depression
0.3-0.4 = 30-40% of risk is due to genetic factors
Medial prefrontal cortex (of those with depression)
Increased functional activity
Lower volume
Lateral prefrontal cortex (of those with depression)
Decreased functional activity
Lower volume
Striatum (of those with depression)
Decreased functional activity
Lower volume
Amygdala (of those with depression)
Increased functional activity
Same volume
Hippocampus (of those with depression)
Increased functional activity
Lower volume
Low Brain Derived Neurotrophic Factor (BDNF) is caused by
Depression
- less dendritic sprouts
5 primary Monoamines
- dopamine (DA)
- norepinephrine (NE)
- serotonin (5HT)
- Melatonin
- Histamine
Monoamines regulate
mood, sleep, appetite, peristalsis, arousal, sexual function, cognition, reward, motivation, aggression – sometimes with opposing effects between dopamine and serotonin.
7 Treatments for depression
- Psychotherapy - cognitive behavioral therapy
- Tricyclic antidepressants (TCA’s)
- Monoamine oxidase inhibitors (MAOi’s)
- Selective Serotonin Reuptake Inhibitors (SSRI’s)
- Serotonin/Norepinephrine Reuptake Inhibitors (SNRI’s)
- Hallucinogens (ketamine, psilocybin, MDMA)
- Electroconvulsive therapy (ECT & TMS)
SNRIs
Venlafaxine (Effexor)
duloxetine (Cymbalta)
- blocks (antagonizes) both SERT and NET.
Bupropion (Wellbutrin)
little action at SERT, but blocks DAT and NET. So not an SSRI or a SNRI – in a class of its own.
Fluoxetine (Prozac)
least selective, first line for adolescents
Paroxetine (Paxil)
anti-cholinergic effects, most weight gain
Citalopram (Celexa)
most selective for SERT
Sertraline (Zoloft)
also antagonist of DAT (dopamine transporter)
SERT
serotonin transporter
NET
norepinephrine transporter
Monoamine Oxidase Inhibitors
removes the neurotransmitters norepinephrine, serotonin and dopamine from the brain.
Serendipitous
discovery that a drug for tuberculosis patients had antidepressant effects
Phenelzine
irreversible inhibitor of monoamine oxidase – once it binds the enzyme it permanently inactivates it and there is no more enzyme until the cell makes more
- Highly effective
Negative side effects of Phenelzine
numerous drug-drug interactions that cause hypertensive crisis (too much adrenaline) & serotonin syndrome (too much serotonin) that can be fatal
Tricyclic antidepressants (TCAs) targets
primary therapeutic benefit is blocking the reuptake of both serotonin and norepinephrine (inhibit NET and SERT)
TCAs are antagonists for
5HT2A, 5HT2C, 5HT6, 5HT7 receptors, a1 adrenergic receptor
2 Main TCAs
- imipramine
- amitriptyline
Half-lives of SSRIs
around 24-30 hours, but fluoxetine is 48-96 hours. Active metabolites have half-lives of several days.
Discontinuation Syndrome of SSRIs
anxiety, insomnia, headache, nausea. Taper off treatment by reducing dose and then taking on alternating days.
Symptoms of Serotonin Syndrome
Agitation or restlessness, hyper-reflexes, diarrhea, fast heart beat and high blood pressure, hallucinations, increased body temperature, loss of coordination, nausea, vomiting
- Can be fatal –hyperthermia, tachycardia, lactic acidosis from muscle contraction.
Causes of Serotonin Syndrome
TOO MUCH SYNAPTIC SEROTONIN
- drug-drug interaction of SSRI + MAOI
- SSRIs + dextromethorphan (cough medicine)
- SSRIs + triptans (migraine medicines) or some opioids (analgesics)
- MDMA
Dysthymia
depressed mood lasting longer but less severe than MDD
Postpartum depression
caused by sudden drop in estrogen/progesterone
Atypical Depression
overeating, oversleeping, ability to react positively to positive events, oversensitivity to rejection
Neuropathic Pain
chronic pain & depression co-morbid
8 Related Disorders that also respond to antidepressants
- Dysthymia
- Postpartum depression
- Atypical depression
- Seasonal Affective Disorder
- Anxiety Disorders
- OCD
- Neuropathic Pain
- Bulimia
4 Hallucinogens that are used as rapid antidepressant
- Ketamine
- Psilocybin
- LSD
- MDMA
antagonist of NMDA type of glutamate receptors - increases spine density within 1 hour of treatment. Given intravenously every 1-4 weeks
Ketamine
converted to psilocin in the body - agonist of 5HT2A serotonin receptor
Psilocybin
agonist of 5HT2A serotonin receptor
LSD (derived from ergot mold)
amphetamine like drug that is selective for SERT - reverse transports serotonin
MDMA
______act as catalyst for treating depression
Hallucinogens
The first antidepressant
Imipramine (first designed as an antipsychotic)
neurogenesis
generation of new neurons
Most commonly used tricyclic antidepressant
amitriptline
