Depression and Mood Disorders Flashcards
What are the risk factors for adult mental illness?
Childhood abuse
Neglect
What are the 8 parts of a mental state exam?
Appearance Behaviour Speech Mood/Affect Thought (form and content [inc. delusions]) Perception Cognition Insight
What important schooling aspects are important in a social history?
Academic performance
Behaviour
Friends
What are important employment aspects are important in a social history?
Jobs:
- Performance
- Sick leave
Reasons for unemployment
What important aspects of relationships are important in a social history?
Length Details Reasons for breakup Children Sexual history
What is a forensic history?
Criminal offences
What are some aspects of assessing general appearance in a mental state exam?
Age Physique/Build Dress (Any evidence of self-neglect?) Effort with appearance Tattoos Signs of physical ill-health Posture Facial expression Physical features of alcoholism or drug abuse
What are some aspects of assessing behavour in a mental state exam?
Describe what they're doing (Appropriate for situation?) Psychomotor agitation/retardation: - Unintentional and purposeless motions - Stems from mentail tension and anxiety Eye contact Attitude/Raport
What are some aspects of assessing quality of speech in a mental state exam?
Clarity
Volume
What are some aspects of assessing of rate of speech in a mental state exam?
Pressure
Poverty
What are some aspects of assessing quantity of speech in a mental state exam?
Too much/little
Spontaneous
Sudden silences
How do we describe mood in a mental state exam?
Objective description
Subjective description
How is mood usually described in a mental state exam?
In patient’s own words
What is afferent?
The experience of feeling or emotion
What parameters can aid in the labelling of afferent?
Appropriateness
Intensity
Range/Reactivity/Mobility
What are the two types of appropriateness in the assessment of affect in a mental state exam?
Congruent (appropriate for emotion in context)
Incongruent (inappropriate)
What can a bland affect on describing a distressing situation indicate?
Schizophrenia
What can a blunted intensity in the assessment of affect in a mental state exam?
Schizophrenia
Depression
PTSD
What can a heightened intensity in the assessment of affect in a mental state exam?
Mania
What can an exaggerated intensity in the assessment of affect in a mental state exam?
Personality disorder
How can the mobility of affect be described in a mental state exam?
Restricted
Labile
Reactive
What is passive suicidality?
Thoughts of life not worth living
What is active suicidality?
Thoughts of wanting to self-harm/die with methods and plans
How can thought form be inferred in a mental state exam?
Speech
Patient’s description
What is flight of ideas (thought form)?
High tempo thoughts Words associated inappropriately due to: - Their meaning - Rhyme Speech loses aim and patient wanders from theme Jump from topics to topic with recognisable links: - Rhyming - Puns - Environmental distractions
What is poverty of thought?
Global reduction in quantity of thought
What are the features of a formal thought disorder?
Evidence in patient's writing/speech that there is abnormal thought linking Disturbance in: - Organisation - Control - Processing NOT a content abnormality ie. Thought A -> Thought B
What is thought blocking? In what condition is it seen in?
Speech suddenly interrupted by silence
Schizophrenia
A patient talks freely but vaguely. Speech is muddled, illogical, difficult to follow and cannot be clarified. A lot is said but no information is gathered.
Loosening of associations
What is tangential thinking?
Wandering from topic and never returning to it
Patient doesn’t provide the info requested
ie. Thought A -> F -> C
What is circumstantiality?
Inability to answer a question without giving excessive and unnecessary detail
Patient will eventually answer
ie. Thought A -> Thought A1 -> Thought A2 -> Thought A
What are neologisms?
Patient makes up a new word or phrase using existing words or phrases in a bizarre way
What are though preoccupations?
Thought content that are not fixed, false or intrusive
BUT have an undue prominence in patient’s mind
What are overvalued ideas?
Unreasonable, sustained beliefs that are held with less than delusional intensity
Give an example of an overvalued idea?
Hypochondriasis
What are obsessions?
Undesired, unpleasant intrusive thoughts that cannot be suppressed
What is a delusion?
A fixed, false belief.
Inappropriate to the patient’s socio-economic background
Firmly held in the face of:
- Logical argument OR
- Evidence to the contrary
Not modified by experience or reason
Usually very individualised or of great personal significance
Where do most delusions originate from?
Often an attempt to explain an anomalous experience as hallucinations
What are grandiose delusions?
Belief that one is very powerful or even a God
What are nihilistic/cotard delusions?
False belief that one does not exist or has died
What are bizarre delusions?
Beliefs that are clearly impossible
Not understood by peers and don’t derive from life experiences
What is a delusion of reference?
Insignificant events/objects have great personal significance
What are delusions of control? What else can they be called?
External forces controlling oneself
Passivity
What are the four main features in assessing perception in a mental state exam?
Derealisation/Depersonalisation: - Perception that surroundings/self aren't real Deja vu Illusions Hallucinations
What do second person auditory hallucinations indicate?
Psychotic depression
What do third person auditory hallucinations indicate?
Schizophrenia
How can we assess attention and concentration (cognition)?
Serial sevens (count down from 100 in sevens) Digit span (give number sequence - ask to recall)
How else can we assess cognition?
Orientation (time/place/person) Memory Calculation Language (name objects) Visuospatial functioning (copy a diagram/clock face) Executive functioning: - Ask what x and y have in common
What are some clues that a patient’s cognition is impaired?
Unable to recall purpose of interview Vague about: - Time - How they came to arrive at interview Discussing past events/dead relatives as if current
How many points are in the Addenbrookes Cognitive Examination?
100
How many points are in the Montreal Cognitive Assessment?
30
What can insight be divided into in terms of the mental state exam?
The four As:
- Awareness of one’s own symptoms
- Attribution of symptoms to appropriate mental disorder
- Appraisal/Analysis of consequences of symptoms
- Acceptance of treatment
What is anautognosia?
Absence of awareness of ones own symptoms
What is dysautoagnosia?
Absence of attribution of symptoms to an appropriate mental disorder
How is early morning wakening described?
Waking >= 2 hours before expected/normal time
What is stupor?
Absence of relational functions
What is anhedonia?
Loss of enjoyment/pleasure
What is appearance and behaviour like in depression?
Reduced facial expression 'Furrowed' brown Reduced eye contact Limited gesturing Difficult rapport
What is speech like in depression?
Reduced rate, volume, intonation
Lowered pitch
Increased speech latency
Limited content (short, brief answers)
What is a patient’s mood like in depression?
‘Flat’
What is a patient’s affect like in depression?
Depressed
Reduced range
Limited reactivity:
- Doesn’t respond/react to changes in subject/context/emotion
How is thought form affected in depressive moods?
Flow of thought:
- Slow and pondering
- Might be absent
How is thought content affected in depressive moods?
Negative, self-accusatory, guilt Delusions may occur: - Guilt - Poverty - Nihilism - Hypochondriasis
What other symptoms tend to be presence alongside paranoia in psychosis?
Persecutory ideas/delusions
Altered perceptions
Lost insight
What types of auditory hallucinations can be present in depressive states?
2nd person and derogatory
What cognitive deficits are typically present in depressive states?
Working memory
Attention
Planning
How is insight affected in depression?
Typically preserved
In what conditions is insight often absent?
Schizophrenia
Mania
What do patients experiencing depression often attribute their symptoms to?
Sins
Physical illness
Personal failing and weakness
What is the lifetime prevalence of depression?
14-18% in lifetime
How many cases of depression become chronic?
20%
How does DSM-5 classify depressive disorders?
Major Depressive Disorder
Persistent Depressive Disorder
How are mood disorders as defined by ICD-10?
F30 - Manic episode F31 - Bipolar affective disorder F32 - Depressive episode F33 - Recurrent depressive disorder F34 - Persistent mood disorders F38 - Unspecified mood disorder
How are depressive episodes defined by ICD-10?
F32.0 - Mild depressive episode
F32.1 - Moderate depressive episode
F32.2 - Severe depressive episode without psychosis
F32.3 - Severe depressive episode with psychosis
F32.8 - Other depressive episodes
F32.9 - Depressive episode, unspecified
What are the diagnostic features of a depressive illness?
Must be clearly abnormal for individual concerned
It must persist
Should interfere with normal function significantly
What are general criteria for depression?
Depressive episode lasting >= 2 weeks
No hypomanic/manic symptoms at any point
What are the core features of depression (criterion B)?
At least 2 of the 3 following present:
- Depressed mood:
- To an abnormal degree
- Present for most of day; almost every day
- Largely uninfluenced by circumstances
- Sustained for at least 2 weeks - Loss of interest/pleasure in normally fun activities
- Decreased energy or increased fatiguability
The following are additional features of depression (criterion C):
- Loss of self-confidence/esteem
- Unreasonable feelings of self-reproach/excessive guilt
- Recurrent thoughts of death/suicide or suicidal behaviour
- Diminished ability to think/concentrare
- Change in psychomotor activity
- Sleep disturbance
- Change in appetite (weight change)
At least 4
What rating scales can be used to assess the severity of depression?
Hamilton Rating Scale for Depression
Montgomery-Asperg Depression Rating Scale
Beck Depression Inventory
How is a moderate depressive episode defined by the F32.0 criteria?
At least 2 of the 3 symptoms in criterion B
Criterion C symptoms:
- Enough present to give total of >= 6
How is a severe depressive episode defined by the F32.0 criteria?
All 3 symptoms from criterion B
Criterion C symptoms:
- Enough present to give total of >= 8
How can we define a somatic syndrome?
Four of the following present:
- Loss of interest in usually pleasurable activities
- Loss of emotional reactions to emotional events
- Early morning waking
- Depression worse in the morning
- Objective evidence of psychomotor retardation
- Marked loss of appetite
- Weight loss (>=5% in last month)
- Loss of libido
What do the following define:
- Mood reactivity
- Two or more of the following:
- Significant weight gain/increased appetite
- Hypersomnia
- Leaden paralysis (heavy feeling in arms/legs)
- Interpersonal rejection resulting in social/occupational impairment
Atypical depression
What is Cotard’s Syndrome?
A type of psychotic depression
What are the features of Cotard’s Syndrome?
Often nihilistic delusions
In what populations is Cotard’s Syndrome more common?
Elderly
What is the median number of lifetime episodes in major depressive disorder?
4
What is the mean age of onset of major depressive disorder?
27 years
What are the five Rs of depression? At what periods do they occur?
Response (acute phase - within 12 weeks)
Remission (at beginning of continuation; 4-9 months)
Recovery (maintenance stage - after 1 year)
Relapse (symptoms again during acute/continuation)
Recurrence (more symptoms after recovery)
How does DSM-V classify Bipolar disorders?
Bipolar:
- I
- II
Cyclothymic disorder
How does ICD-10 classify Bipolar disorders?
Hypomania
Mania with psychotic features
Mania without psychotic features
How is Bipolar I defined by DSM-V?
Has to meet criteria for mania
Represents ‘classic’ form of manic-depressive psychosis
How is Bipolar II defined by DSM-V?
Current/past hypomania AND current/past depression
No mania
What is the most common kind of Bipolar disorder (in terms of DSM-V classification)?
Bipolar II
What is Bipolar II.5 in terms of DSM-V?
Depressions superimposed on cyclothymic temperament
How is Cyclothymic disorder described in the context of DSM-V?
- Cycles of hypomania/depression over at least 2 years
- Never asymptomatic for more than 2 months during those 2 years
- No major depression/mania
- No schizoaffective disorder
- Not explained by drugs.alcohol
- Symptoms impair functioning
What is Bipolar III?
‘Psuedo-unipolar’
Hypomania ONLY after use of antidepressants for depression
What is Bipolar IV?
Depressions arising from a hyperthymic temperament
How is Bipolar Affective Disorder described in ICD-10?
Characterised by >=2 episodes in which mood and activity are significantly disturbed:
- Hypomania/Mania and sometimes depression
- Repeated hypomania or mania ONLY
- 1st episode of (hypo)mania -> Not depression
How does ICD-10 describe a hypomanic episode?
- Mood is elevated/irritable
- To an abnormal degree
- Sustained for >=4 consecutive days - > =3 of the following; interfering with daily living:
- Increased activity/restlessness
- Increased talkativeness
- Difficulty concentrating or distractability
- Reduced need for sleep
- Increased sexual energy
- Mild spending sprees
How does ICD-10 describe a manic episode?
- Mood predominantly elevated/expansive/irritable:
- Definitely abnormal
- Prominent change sustained for >=1 week
- Or prominent change requiring hospital admission - > =3 of the following (>=4 if only irritable) resulting in severe interference:
- Restlessness
- Pressure of speech
- Flight of thoughts
- Disinhibition
- Reduced need for sleep
- Grandiosity/Increased self-esteem
- Distractability
- Reckless behaviour without appreciating risk
- Marked sexual energy/indiscretions
What is F30.1?
Mania without psychotic symptoms
Perceptual disorders may occur:
- Subacute hyperacusis
- Appreciations of colours as very vivid
What is F30.2?
Mania with psychotic symptoms
What delusions or hallucinations must not occur in F30.2?
Those listed as Typical Schizophrenic:
- No bizarre delusions
- No 3rd person/running commentary hallucinations
What are the commonest delusions in mania with psychotic symptoms?
Grandiose
Self-referential
Erotic
Persecutory
When does bipolar disorder tend to onset?
Late teens/early 20s
If there is a family history of bipolar disorder, how does this affect onset of bipolar disorder?
Earlier
Precipitated by lower levels of stress
Bipolar disorder that onsets after 60 years of age is often associated with what?
Treatment resistance
Progressive decline in functioning
Underlying organic cause
What gene is associated with Schizophrenia?
DISC2
What genes are associated with Schizoaffective disorders?
NRG1
G72
G30
What gene is associated with bipolar disorder?
ANK3
What is the most common mood disturbance in bipolar disturbance?
Depression (30-50%)
What ICD-10 range defines eating disorders?
F50-F59
What is F50.0?
Anorexia nervosa
What is F50.1?
Atypical anorexia nervosa
What is F50.2?
Bulimia nervosa
What are the four features of anorexia nervosa?
- Weight loss (lack of weight gain in kids):
- Weight =<15% below normal for age and height - Weight loss in self-induced by fatty-food avoidance
- Self-perception of being too fat (intrusive dread of fatness)
- Widespread endocrine disorder:
- Involves hypothalamic-pituitary-gonadal axis
- Amenorrhoea in females (vaginal bleed while on HRT/COC)
- Loss of libido and potency in males
How can pre-pubertal onset of anorexia nervosa affect development?
Growth ceases In girls: - Breasts do not develop - Primary amenorrhoea In girls: - Genitals remain juvenile
On recovery of pre-pubertal anorexia nervosa, what can occur?
Puberty usually completed normally
Menarche is late
What are the DSM-V subtypes of anorexia nervosa?
Restricting
Binge-eating/Purging
What are the four ICD-10 criteria for Bulimia Nervosa?
- Recurrent overeating:
- >=2 times a week over >=3 months
- Lots of food in a short period of time#2. - Preoccupation with eating and cravings
- Counteracting the fattening effects by >=1 of:
- Self induced vomiting
- Self induced purging
- Alternating periods of starvation (use of appetite suppressants/thyroid hormones/diuretics or abandoning insulin in diabetics) - Self-perception of being too fat
In terms of DSM-V, how many associated features must occur alongside binge episodes to diagnose a binge eating disorder?
> =3
What are some high risk indicative behavioural features for anorexia?
Feeding problems
Reduced BMI
Social difficulties
What are some high risk indicative psychobiological features for anorexia?
Reduced reward and increased threat
Sensitivity
Social cognition problems
Cognitive rigidity
What are some prodromal features of anorexia?
Coping: - Avoidance - Perfectionism Compulsivity Anxiety
What can indicate a severe enduring anorexia?
Social isolation Impaired physical and mental QoL Habits not goal-directed Threat sensitivity Reduced social cognition
What are some high risk indications for bulimia?
Robust feeding
Increased BMI
Increased reward sensitivity
Reduced response inhibition for food
What is the Standardised Mortality Ratio?
Ratio between number of deaths in a study population and the number of deaths that would be expected?
What is the Standardised Mortality Ratio for anorexia?
5.86
What is the Standardised Mortality Ratio for bulimia?
1.93
What causes refeeding syndrome?
Depletion of already inadequate stores of nutrients:
- Magnesium
- Potassium
- Phosphate
What is a low-moderate risk BMI?
17.5-16
What is a moderate risk BMI?
16-15
What is a high risk BMI?
14.9-13
What is a very high risk BMI?
<13
What do the BMA Guidelines for consenting to treatment say a patient should be able to do?
- Understand in simple language what the treatment is, its purpose and nature and why its propose
- Understand its benefits, risks and alternatives
- Understand broadly the consequences of no therapy
- Retain info long enough to weigh up options and make a decision
What is the purpose of the Adults with Incapacity (Scotland) Act 2000?
Provides guidance for safeguarding the welfare/finances of adults who lack capacity:
- Mental illness
- Learning disability
- Inability to communicate
How does the Adults with Incapacity Act define an adult?
Aged >=16 year
What is Part 6 of the Adults with Incapacity Act?
Welfare/Financial Guardianship:
- Authorises a person to make a decision which the patient can’t
What is Part 5 of the Adults with Incapacity Act?
Medical treatment
When is a person not deemed to have a mental disorder and so won’t be treated as such?
Promiscuity
Sexual deviancy
Alcohol/Drug abuse
Acting as no prudent person would
What does Section 47 prohibit?
Use of force unless immediately necessary and only for as long as is necessary
What article of the European Convention on Human Rights protects against arbitrary detention?
Article 5
When would Emergency Detention be used under the Mental Health Act?
If there is need for an urgent assessment of the patient’s condition when they post a risk to themselves or others
Who can authorise Emergency Detention under the Mental Health Act?
Any doctor (Preferably under guidance by a mental health officer)
How long can a person be detained under an Emergency Detention under the Mental Health Act?
72 hours maximum
Does Emergency Detention under the Mental Health Act allowed the patient to be treated against their will?
No
When would Short-Term Detention be used under the Mental Health Act?
When it is deemed that the patient requires admission to hospital to prevent injury to themselves or others
AND
That there is a need for the provision of medical treatment
Who can authorise Short-Term Detention under the Mental Health Act?
Recommended by a psychiatrist and agreed by a mental health officer
How long can a person be detained under Short-Term Detention under the Mental Health Act?
28 days
Does Short-Term Detention under the Mental Health Act allowed the patient to be treated against their will?
Yes
When would a Compulsory Treatment Order be used under the Mental Health Act?
The patient has a mental disorder in which treatment:
- Would prevent it worsening OR
- Alleviate symptoms/effects
AND
If the patient wasn’t treated there would be risk to:
- Health/safety/welfare of patient
- Safety/welfare of others
How can a Compulsory Treatment Order be approved?
A mental health officer must apply to a Tribunal
The application should have:
- Two medical recommendations
- Plan of care (detailing care and treatment proposed)
Who is allowed to object to anything under the Compulsory Treatment Order?
The patient
The patient’s named person
The patient’s primary carer
Are patient’s upon which a Compulsory Treatment Order has been enforced allowed to be detained in hospital?
Not initially
There will be specifications in the order where detention can be authorised
How long can a Compulsory Treatment Order last?
6 months initially
Can be extended for another 6 months
Then for another 12 months
Under what age does a person categorically have no consent?
If =<12 years
When might children younger than 16 have capacity?
They understand nature/purpose/consequences of intervention
They understand consequences of not having treatment
If a child, deemed competent by a doctor, consents to treatment that their parents do not consent to, can the parents overrule the decision?
No.
If a child, deemed competent by a doctor, does not consent to treatment that their parents do consent to, can the parents overrule the decision? What can they do?
No.
Can potentially apply for a court order
If a child, deemed competent by a doctor, does not consent to treatment that you, as their physician deem life-saving, what should you do?
Discuss with MDT
Legal advice might be useful - a court order may be required
If parents of a child who is not competent (younger than 12 or cannot understand fully the procedure) do not consent to treatment that physicians deem beneficial to the child’s survival or QoL, what should you do?
MDT discussion
Legal advice
Court order
What antidepressants are deemed NA-selective?
Maprotiline
Protriptyline
Nortriptyline
What antidepressants are deemed non-selective?
Amitriptyline and Imipramine (1:1 ratio)
Clomipramine
What antidepressants are deemed serotonin-selective?
Venlafaxine Paroxetine Sertraline Fluoxetine Citalopram
What class of drugs do Phenelzine, Isocarboxazid and Tranylcypromine belong to?
MAOI
What type of drug is Moclobemide?
Reversible Inhibitor of MonoAmine oxidase A (RIMA)
Give some examples of TCAs
Amitriptyline Clomipramine Imipramine Nortriptyline Dosulepin
Give some examples of SSRIs
Fluoxetine Paroxetine (Es)Citalopram Sertraline Fluvoxamine
Give some examples of SNRIs
Venlafaxine
Duloxetine
What type of drug is Reboxetine?
NARI
What type of drug is Mirtazapine?
An atypical antidepressant with NA and specific serotenergic activity (NASSA)
What systems function to mediate seeking and approach behaviours (including pleasure)?
Ascending DA systems (mesolimbic/cortical)
Ventral striatum
What is the dorsal striatum important for?
Movement
What is the amygdala important for?
Conditioning and learning
What is the function of the anterior cingulate?
Attention
Conflict
Response selection
What part of the brain is responsible for relative reward preference and rule learning?
Orbitofrontal cortex
What systems function to promote survival in event of threat?
Ascending serotonin systems NA transmitters Central nucleus of amygdala Hippocampus Ventroanterior and medial hypothalamus Periaqueductal grey matter
What do MAOIs prevent?
The action of monoamine oxidase which breaks down:
- DA
- NA
- Serotonin
How do TCA work?
Act at presynaptic membrane to prevent serotonin and NA reuptake
In dopamine transmission, how is dopamine produced?
Tyrosine -> Levodopa -> DA
What effect do amphetamines and MPP+ have on the DA transporter and dopamine?
Compete with DNA for reuptake
Force DA out of presynaptic vesicles, resulting in their release into synapse
What effect do cocaine, GBR 12935, WIN 35,428 and RTI-121 have on the DA transporter?
Bind to receptor and inhibit DA reuptake
How is NA produced in a noradrenergic neurone?
Tyrosine -> L-DOPA -> DA (cytoplasm) -> DA (vesicle) -> NA
How does amphetamine affect the NA transporter (NET)?
Substrate
Reverses direction of neurotransmitter
Increases synaptic NA
What drugs inhibit the NA transporter?
Cocaine
Nisoxetine
Reboxetine
How is serotonin produced in a serotonergic neurone?
Tryptophan -> 5-Hydroxytrytophan -> Serotonin
How does amphetamine and MDMA affect the serotonin transporter?
Substrates
Competitive reuptake inhibiton
What drugs inhibit the serotonin transporter?
Cocaine
Fluoxetine
Paroxetine
Sertraline
What are the mechanisms by which amphetamine and MDMA increase synaptic concentrations of DA/NA/5-HT?
VMAT2 inhibitors:
- Reduce their transport in vesicles by forcing them out of the vesicles
- Increase concentration in presynaptic neurone
TAAR1 agonists:
- Trigger protein kinases A and C
- Phosphorylate DAT/NET/SERT
- Reverse transport direction
- Increas concentration in synaptic cleft
What enzyme converts tryptophan to 5-hydroxytryptophan?
Tryptophan hydroxylase
What enzyme converts 5-hydroxytryptophan to serotonin?
Aromatic-L-amino acid decarboxylase
What serotonin receptors are targeted by anti-depressants?
5-HT1a 5-HT2a 5-HT2b 5-HT2c 5-HT3 5-HT6 5-HT7
What drugs target 5-HT1b and 5-HT1d?
Migraine medications (eg. Triptans)
What serotonin receptor is targeted by anti-emetics?
5-HT3
What serotonin receptor has GI pro-kinetic effects and what is it used to treat?
5-HT4
IBS and chronic constipation
On what receptor do fluoxetine and paroxetine at on?
5-HT2 (a-c)
On what receptors does Amitroptyline act on?
5-HT6
5-HT7
How long do SSRIs take to have effect? At this time, what are the levels of 5-HT like in the synaptic cleft?
2-3 weeks
Normal
What circuits are indicated in SSRI use?
Limbic-cortical
What type of receptors are 5-HT1a receptors?
Inhibitory autoreceptors
Upon acute antidepressant treatment, what happens in the synapse?
5-HT reuptake is inhibited
Increased [5-HT] in cleft
Stimulates 5-HT1a receptors to inhibit presynaptic firing
What does chronic occupancy of the 5-HT1a receptor cause?
Desensitise it
Return to normal firing
Facilitates serotenergic transmission in presence of reuptake blockade
What is wrong with the serotenergic system in depression?
Dysregulation in transmission
Serotonin is not low
Why are SSRIs typically first line?
Almost all can be started at a therapeutic dose
Usually good tolerance
Relatively safe in overdose
Why do SSRIs interact with other drugs?
Inhibit CYP450
What are some side effects of SSRIs?
Sexual dysfunction:
- Via DA blockade +/or serotonin activation
GI side effects (nausea, constipation, diarrhoea)
Short-term anxiety
Increased risk of self-harm in first few weeks in young people (=<25 years)
What drugs can cause reversal of an SSRI?
5-HT2 antagonists
Partial 5-HT1a agonists (eg. Trazodone)
When might an SSRI be avoided?
Agitated depression
Intolerable GI effects
On warfarin (SSRIs can potentiate bleeding)
If on AEDs
When is citalopram specifically avoided?
With another medication that may prolong QT
If diagnosed with long QT
If cardiac disease
If on antipsychotics
If on amitriptyline (for neuropathic pain)
What drug for depression may be preferred in breastfeeding? (This is also the second choice SSRI in all with depression)
Sertraline
What is the typical dosing regime for fluoxetine?
20mg/day PO initially
Increased after 3-4 weeks if necessary
Max 60mg/day PO
What is the typical dosing regime for sertraline?
50mg/day PO initially
Increased by 50mg increments at intervals of at least one week
Max 200mg/day PO
What monitoring may be needed in high does TCA therapy and why?
ECG
QT lengthening
What are the side effects of TCAs?
Constipation Dry mouth Blurred vision Effects on cardiac function Postural hypotension: - Failure of peripheral orthostatic reflexes
What does MAO A metabolise?
NA
5-HT
Tyramine
What does MAO B metabolise?
DA
Tyramine
Phenylethylamine
When are MAOI used?
3rd or 4th line
Often in atypical depression
What are side effects of MAOI therapy?
Flushing
Headache
Hypertension
CVA (rarely)
Why do MAOIs cause their side effects?
Tyramine is usually inactivated in the gut
Since it remains active, NA is released
What can cause hypersensitive crises with MAOI therapy?
Tyramine-containing foods: - Cheese - Yoghurts - Meat - Alcohol Drugs: - Sympathomimetics (OTC cold remedies) - Pethidine
How can the side effects of MAOIs be treated?
Alpha-blockade:
- Phentolamine
- Chlorpromazine
What side effects can some antidepressants (eg. Paroxetine) cause?
Extrapyramidal (due to effects on DA):
- Tremor
- Dystonia
- Akathisia
- Tardive dyskinesia
Give an example of an antipsychotic that may be an antidepressant at a low dose.
Flupentixol
What drug acts as a benzodiazepine receptor inverse agonist on the GABAa receptor complex?
FG-7142
What drug acts as a benzodiazepine receptor antagonist on the GABAa receptor complex?
Flumazenil
What drug acts as a benzodiazepine receptor agonist on the GABAa receptor complex?
Diazepam
When is a benzodiazepine receptor antagonist used?
Reversal of sedative effects benzodiazepine
OR
Treatment of benzodiazepine overdose
What effect does Picrotoxin have on the GABAa receptor?
Binds to the picrotoxin site:
- Channel blocker
- Stimulant and convulsant effects
What other sites (and hence drugs) are on the GABAa receptor (apart from BZD and GAPA sites)? What effects do these have?
Barbituate site
Steroid site
Positive allosteric modulators:
- Indirectly affects agonist or inverse agonist action
What type of receptor is GABAa?
Ligand-gate ion channel
What drugs act as GABAa receptor agonists?
Ethanol
Benzodiazepines
Propofol
Anaesthetics
What drug acts as a GABAa receptor antagonist?
Flumazenil
What type of receptor is GABAb?
GPCR
What drugs act as GABAb receptor agonists?
Baclofen
Propofol
What anticonvulsants act as mood stabilisers?
Carbamazepine
Valproate
Lamotrigine
What second generation antipsychotics can be used as mood stabilisers?
Olanzapine
Risperidone
Aripiprazole
Quetiapine
What other drugs can be used as mood stabiliers?
Lithium carbonate (citrate) Nimodipine (calcium channel blocker)
How does lamotrigine work?
Blocking sodium channels
Doesn’t work directly via GABA:
- Reduces excitability and cell firing
How many lithium work?
Inhibition of 5-HT autoreceptors Increase in anti-apoptotic factor Bcl-2 Inhibition of glycogen synthase kinase-3 (GSK-3) Depletion of inositol Up-regulation of glutamate reuptake
How do true/1st generation antipsychotics work?
Related to D2 receptor affinity
What circuit results in the desired effect of true/1st generation antipsychotics?
DA blockade in the mesolimbic circuits
What causes the adverse effects of true/1st generation antipsychotics?
DA blockade in nigrostriatal pathway:
- Movement disorders
DA blockade in the tubero-infundibular pathway:
- Hyperprolactinaemia
What are the three mechanisms of action of 2nd generation antipsychotics?
- Increased D2 receptor-binding affinity:
- Increased antipsychotic effectiveness - Increased 5-HT2c and a receptor-binding affinities:
- Increased antipsychotic efficacy - Increased 5-HT1a binding affinity:
- Reduced antipsychotic efficacy
What does structural imagine in bipolar disorder show?
Reduced grey matter volume in Brodmann Area 24 (anterior cingulate gyrus)
What does functional imaging in bipolar disorder show?
Increased metabolism in amygdala: - Correlates with outcome Reduced metabolism: - OfC - Medial ventral pfC