L11 - depression and antidepressants Flashcards
define depression
chronic, constant, non specific, life limiting sadness
how is depression diagnosed
no single objective test, use
DSM-IV (diagnostic statistical manual)
and
ICD-10 (international classification of diseases)
based on interview by doctor
describe how the DSM-IV diagnoses depression
5 or more of the following symptoms present in the same 2 week period that exhibit a change from normal fucntioning:
at least one of the following
- depressed mood
- diminished interest or loss of pleasure
remaining from
- significant weight loss
- insomnia
- agitation
- fatigue
- feelings of worthlessness
- diminished ability to think / concentrate
- recurrent suicidal thoughts
why is depression difficult to diagnose
wide variety of symptoms can be reported
difficult to differentiate normal mood changes from depression
depression doesnt present 24/7, might have good days
no single objective test to diagnose
list causes for depression
genetic
environmental
age
expand on genetic causes for depression
40-50% of MZ twins will suffer from depression if their twin does
depression affects 2x as many females as males
list some physiological symptoms of depression
insomnia
fatigue
reduction in self hygiene
expand on environmental causes of depression
- could be life events, eg loss of loved one, job, social isolation
- could also be due to co-morbidities, such as
- terminal / chronic illness
- drug abuse
- anxiety
- neurological disease / illnesses
expand on age as a cause for depression
age for depression onset is decreasing, why?
- life more stressful?
- better at diagnosis?
what are the two types of depression
unipolar -> mood swings in one direction - of sadness
bipolar -> mood fluctuations between depression and mania
does bipolar or unipolar depression have a stronger genetic influence?
bipolar
what are the types of unipolar depression and explain them
describe symptoms of mania (bipolar depression)
present for at least 1 week and impair individuals normal life
- erratic impulsive behaviours
- rapid speech
- poor desicions based on unrealistic thoughts
- short attention span
- reduced sleep / tiredness
- racing thoughts
- elevated / irritable mood
list the types of bipolar disorder and briefly describe them
- cyclothymic disorder (most mild) -> slight depressive states followed by moderate manic states
- bipolar 2 disorder -> small manic states and comparably larger, major depressive states
- bipolar 1 disorder -> severe manic states followed by severe depressive states
individuals with bipolar 1 can also experience mixed affective episodes -> concurrent episodes of mania and depression (highest risk of suicide)
all types cyclic, depressive follows manic
what are the 3 theories of depression
- monoamine theory
- neuroendocrine theory
- neuroplasticity theory
what is the monoamine theory of depression
serotonin levels are responsible for depression
what is the evidence for the monoamine theory of depressoon
- reserpine blocks VMAT2 blocking the uptake of 5-HT into vesicles - and so decreasing [5-HT] in synaptic cleft from reduced exocytosis
The use of reserpine induces depression - antidepressants increase serotonin (and sometimes other amines) in the brain reversing depression symptoms
what limits the monoamine theory for depression
although increasing 5-HT can improve symptoms there is no definitive evidence that 5-HT is deficient in depressed individuals
describe the neuroendocrine theory of depression
- NA and 5-HT neurones input to hypothalamus which causes release of CRH (corticotrophin releasing hormone)
- CRH acts on pituitary inducing release of ACTH (adrenocorticotrophic hormone)
- ACTH causes cortisol release from adrenal cortex in response to increased [ACTH] in blood
- Cortisol associated with stress
describe neuroplasticity (neurodegeneration) theory of depression
Evidence of neuronal loss and decreased neuronal activity in hippocampus ad prefrontal cortex
Anti-depressants and ECT (electroconvulsive therapy) promote neurogenesis in these regions
list the treatments for unipolar depression
SSRIs / SNRIs
MAOIs and TCAs (older)
CBT (first line)
ECT (severe)
list treatments for bipolar depression
CBT Lithium anticonvulsants antipsychotics ECT (severe cases)
describe mechanism of SSRIs
- block SERT - reduces 5-HT uptake
- increased [5-HT] in cleft
- increased activation of 5-HT receptors
give examples of SSRIs
sertraline
fluoxetine
describe mechanism of SNRI
serotonin and noradrenaline reuptake inhibitors
- block SERT and NET
- increase [5-HT] and [NA] in cleft
- increase NA and 5-HT receptor activation
NA significant for energy levels
give example of SNRI
duloxetine
describe TCA mechanism
- block NET>SERT, also block histamine and muscarinic receptors
- increase [NA] and [5-HT] in cleft increasing receptor activation
give examples of TCAs
amitryptyline
imipramine
describe mechanism of MAOIs
- block metabolism of 5-HT, NA,DA in synapse
- increases the [NT] in the synapse to be released by exocytosis
- increased [NT] in synapse and increased receptor activation
give example of a MAOI
selegiline
why are TCAs and MAOIs less used for the treatment of depression now?
they have more off target effects and so possibility for more side effects
describe the mechanism for lithium in bipolar depression treatment
mechanism not entirely understood but believed to be due to:
- Li and Na have same no. of valence electrons so may be able to mimic the role of Na in signal transduction, but at a slower reduced effect due to it being smaller and less electronegative ( so it slows down the transmission and treats manic stages)
- seems to also increase 5HT synthesis but decrease NA release
why is amitriptyline especially useful in some cases of depression
amitryptyline low dose is used to treat pain but also inhibits NET and SERT, so would be a good option for individuals experiencing depression due to chronic pain as it treats both
side effects of lithium treatment
- nephrotic toxicity
- teratogenic -> can cause birth defects if taken by pregnant women
- induces hyperthyroidism
- dehydration
- too much can lead to overdose -> is it sensible to give depressed patients a substance that can cause overdose?
many other side effects
what can be given alongside lithium treatment to prevent hyperthyroidism
thyroxine
what can be given alongside lithium treatment to prevent hyperthyroidism
thyroxine (hormone containing iodine)
describe anticonvulsants for bipolar depression treatment
what is the most suitable treatmnet for pregnant women with bipolar depression
antipsychotics
what is the most suitable treatmnet for pregnant women with bipolar depression
antipsychotics
why arent typical antipsychotics used in bipolar depression tretament?
they are more anti-manic than mood stabilising, they may worsen depressive episodes
what is the commonly prescribed antispsychotic for bipolar depression
olanzapine (atypical)
what is a problem with bipolar disorder diagnosis
often misdiagnosed as depression, and antidepressants prescribed
these can worsen manic episodes (due to increased NA,DA, 5-HT)
explain CBT
aims to change thinking processes and perspectives to have a more positive, open mindset
first line treatment before drugs
explain ECT
inducing epileptic seizures in cases where symptoms are most severe
describe pathology of depression (changes to brain)
enlarged ventricles
shrunken pre frontal cortex and hippocampus
