HTHSCI 2H03 - 9.1 Drugs for Mood Disorders

What are the three major classes of neurotransmitters?

small molecule neurotransmitters

neuropeptides

neurotransmitters

small molecule neurotransmitter examples

acetylcholine

monoamines (dopamine / norepinephrine / epinephrine / serotonin)

amino acids (glutamate / GABA)

acetylcholine (location, effects, clinical significance)

location: involved in memory and widely distributed in the CNS (a major transmitter in the ANS)

effects: CNS → excitatory or inhibitory; controls voluntary skeletal movement

ANS → activates parasympathetic nervous system

clinical use: myasthenia gravis + alzheimer's disease (loss of memory)

monoamine → dopamine (location, effects, clinical significance)

location: basal ganglia and limbic system

effects: usually excitatory (locomotion, attention, learning, and the reinforcing effects of abused drugs)

clinical significance: parkinson's disease and schizophrenia

monoamine → epinephrine (clinical significance)

clinical significance: bipolar disorder, and major depression

monoamine → norepinephine (location, clinical significance)

location: widely distributed in CNS; a major transmitter in the ANS

clinical significance: bipolar disorder and major depression

monoamine → serotonin (location, effects, clinical significance)

location: brainstem, limbic system, GI tract, platelets

effects: receptor subtype specific

clinical significance: anxiety, bipolar disorder and major depression

amino acid → glutamate (location, effects, clinical significance)

location: widely distributed in the CNS

effect: highly excitatory and most commonly inhibits CNS neurotransmitters

clinical significance: memory

amino acid → GABA (location, effects, clinical significance)

benzodiazepines

location: widely distributed in the CNS

effect: highly excitatory and most commonly inhibits CNS neurotransmitters

clinical significance: seizure and anxiety disorders

Neurotransmitter Systems

noradrenergic system & serotonergic system

what enzyme is the the neurotransmitter systems metabolized by?

enzyme monoamine oxidase (MAO) in the brain

Noradrenergic system (what is it + purpose)

norepinephrine and epinephrine

2 receptor classes: alpha and beta adrenergic receptors

maintains emotional tone (mood, arousal, altertness / wakefulness)

noradrenergic system (how does it work?)

neurons originate from the locus cerelus project to limbic system & cerebral cortex

Serotonergic System (what is it + its purpose)

serotonin

many receptor classes with subtypes for each

maintains sleep-wake cycles, emotional tone and sensory perception (pain)

Serotonergic System (how does it work)

neurons originate in raphe nuclei project to the limbic system and cerebral cortex (co-localized with noradrenergic system)

what does a decrease in serotonergic tone indicate?

pain / depression

mood disorders

persistence disturbances in mood that impairs person's ability to effectively engage in normal ADLs that are stand alone

depression

associated with an imbalance of neurotransmitters (noradrenaline and serotonin) in regions associated with focused cognition and emotion

Major Depressive Disorder DSM-5TR

five or more of the following symptoms during the same 2 week period with at lease one being depressed mood or loss of interest or pleasure

1. (has to be) depressed mood most of the day OR

2. (has to be) markedly diminished interest or pleasure in all (or almost all) activities (andonia)

3. significant changes in weight or appetite

4. insomnia or hypersomnia

5. psychomotor agitation or retardation

6. fatigue or loss of energy

7. feelings of worthlessness or excessive or inappropriate guilt

8. diminished ability to think or concentrate, or indecisiveness

9. recurrent thoughts of death and suicidal ideation

antidepressant drugs

treats depression by enhancing, elevating or stabilizing mood and are used to treat all symptoms of major depressive disorder as well as the depressive phases of bipolar 1 disorder

exerts their effects through actions on serotonin, norepinephrine and dopamine

what else can antidepressant drugs be used to treat?

anxiety disorders & obsessive-compulsive

physiological and physical signs of pain and effective in patients without major depressive disorder (neuropathic pain)

management of children enuresis (bedwetting)

caution with antidepressant drugs use

those under 25 should be monitored closely for warning signs for self-harm and suicide, especially at the start of treatment

antidepressants drugs (drug classes)

SSRI → selective serotonin reuptake inhibitors (most commonly prescribed for major depression)

atypical antidepressants → including SNRIs (serotonin, NE reuptake inhibitors

tricyclic antidepressants → TCAs (multi-use)

monoamine oxidase inhibitors → MAOIs (inhibit metabolism of monoamine, increasing the tone of them in the brain

SSRIs (selective serotonin reuptake inhibitors)

typical antidepressant

inhibits reuptake of serotonin at the synapse (presynaptic serotonergic receptors) allowing serotonin to persist in the synapse for longer

presynaptic 5HT receptors become less sensitive, postsynaptic receptors become more synaptic

when do we see the effects of SSRIs?

although we see a rise in serotonin levels immediately, the effect of mood changes are not seen until much later

AE of SSRIs

has no affinity for histamine, alpha adrenergic or muscarinic receptors

sexual dysfunction

nausea

headache

weight gain

anxiety / nervousness

akathisias (inability to remains still)

sleep disturbances (due to activation of the CNS)

increase bleeds (inhibit platelet aggregation)

discontinuation of SSRIs

should be gradual to try and minimize withdrawl effects (N, dizziness, lethargy, anxiety, tremor)

serotonin syndrome

pharmacodynamic drug drug interaction that occurs when someone who takes SSRIs and another drug that increases serotonin levels

causes extreme serotonin levles

serotonin syndrome effects

mental status change (confusion, anxiety)

HTN

tremors

sweating

hyperpyrexia

ataxia

atypical antidepressants

SNRIs and NDRIs

SRNIs

inhibits reuptake of serotonin and NR to elevate mood; symptoms may improve earlier than other drugs

can also be effective in the management of the neuropathic pain

NDRIs

norepinephrine and dopamine reuptake inhibitors

less likely to induce sexual dysfunction, weight gain or insomnia

tricyclic antidepressant drugs

used for refractory cases of depression when patients are not responding to the rest

inhibits the reputake of NE, serotonin and dopamine into presynaptic neuron, increasing its levels in the synapse

Tricyclic Antidepressant Drugs affinity for other

has affinity for histaminergic, muscarinic and alpha 1 adrenergic receptors

AE of tricyclic antidepressant drugs

sedation

blurred vision

dry mouth

urinary retention

constipation

tachycardia

orthostatic hypotension

monoamine oxidase inhibitor drugs

metabolizes dopamine, norepinephrine and serotonin

inhibition of MAO enzyme increases nomoamine levels

Used to treat depression when TCAs, SSRIs or SNRIs are not effective (refractory cases)

monoamine oxidase inhibitor drugs AE

orthostatic hypotension

headache

insomnia

diarrhea

bipolar 1 disorder

characterized by at least 1 lifetime manic episode

most clients also experience major depressive episodes over the course of their lives

manic episode

mood stabilizers

lithium

anticonvulsant drugs

antipsychotic drug

atypical antipsychotic drugs

management of mania, major depressive disorder, schizophrenia

easily tolerable

lithium use monitoring

Serum levels must be monitored 5 days post any change in regimen

12-hour serum level every 3 months

Creatinine, urinalysis every 3-6 months

Clients encouraged to drink 2-3 liters fluid per day

Take at bedtime: protective of kidneys (nephrogenic diabetes insipidus)

Always take SDoH into considerations

lithium toxicity

muscle weakness

lack of coordination

vomiting

diarrhea tremor

twitching

lethargy

mental confusion

polyuria

anticonvulsant drugs

reached for this due to lithium being very hard to take for some

AE of anticonvulsant drugs

dizziness

drowsiness

headache

nausea

blurred vision

sedation

lithium

vital to address the manic episodes to help them stabilize their mood (lithium is hard to tolerate)

used for the treatment of mania and reducing the frequency and magnitude of mood changes in episodes experienced

encourage to take bedtime to reduce nephrotoxicity (can happen locally at kidneys) → causes drug induced diabetes insipidus