Depression and Mood Disorders Flashcards
(246 cards)
1
Q
What are the risk factors for adult mental illness?
A
Childhood abuse
Neglect
2
Q
What are the 8 parts of a mental state exam?
A
Appearance Behaviour Speech Mood/Affect Thought (form and content [inc. delusions]) Perception Cognition Insight
3
Q
What important schooling aspects are important in a social history?
A
Academic performance
Behaviour
Friends
4
Q
What are important employment aspects are important in a social history?
A
Jobs:
- Performance
- Sick leave
Reasons for unemployment
5
Q
What important aspects of relationships are important in a social history?
A
Length Details Reasons for breakup Children Sexual history
6
Q
What is a forensic history?
A
Criminal offences
7
Q
What are some aspects of assessing general appearance in a mental state exam?
A
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
8
Q
What are some aspects of assessing behavour in a mental state exam?
A
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
9
Q
What are some aspects of assessing quality of speech in a mental state exam?
A
Clarity
Volume
10
Q
What are some aspects of assessing of rate of speech in a mental state exam?
A
Pressure
Poverty
11
Q
What are some aspects of assessing quantity of speech in a mental state exam?
A
Too much/little
Spontaneous
Sudden silences
12
Q
How do we describe mood in a mental state exam?
A
Objective description
Subjective description
13
Q
How is mood usually described in a mental state exam?
A
In patient’s own words
14
Q
What is afferent?
A
The experience of feeling or emotion
15
Q
What parameters can aid in the labelling of afferent?
A
Appropriateness
Intensity
Range/Reactivity/Mobility
16
Q
What are the two types of appropriateness in the assessment of affect in a mental state exam?
A
Congruent (appropriate for emotion in context)
Incongruent (inappropriate)
17
Q
What can a bland affect on describing a distressing situation indicate?
A
Schizophrenia
18
Q
What can a blunted intensity in the assessment of affect in a mental state exam?
A
Schizophrenia
Depression
PTSD
19
Q
What can a heightened intensity in the assessment of affect in a mental state exam?
A
Mania
20
Q
What can an exaggerated intensity in the assessment of affect in a mental state exam?
A
Personality disorder
21
Q
How can the mobility of affect be described in a mental state exam?
A
Restricted
Labile
Reactive
22
Q
What is passive suicidality?
A
Thoughts of life not worth living
23
Q
What is active suicidality?
A
Thoughts of wanting to self-harm/die with methods and plans
24
Q
How can thought form be inferred in a mental state exam?
A
Speech
Patient’s description
25
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
```
26
What is poverty of thought?
Global reduction in quantity of thought
27
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
```
28
What is thought blocking? In what condition is it seen in?
Speech suddenly interrupted by silence
| Schizophrenia
29
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
30
What is tangential thinking?
Wandering from topic and never returning to it
Patient doesn't provide the info requested
ie. Thought A -> F -> C
31
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
32
What are neologisms?
Patient makes up a new word or phrase using existing words or phrases in a bizarre way
33
What are though preoccupations?
Thought content that are not fixed, false or intrusive
| BUT have an undue prominence in patient's mind
34
What are overvalued ideas?
Unreasonable, sustained beliefs that are held with less than delusional intensity
35
Give an example of an overvalued idea?
Hypochondriasis
36
What are obsessions?
Undesired, unpleasant intrusive thoughts that cannot be suppressed
37
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
38
Where do most delusions originate from?
Often an attempt to explain an anomalous experience as hallucinations
39
What are grandiose delusions?
Belief that one is very powerful or even a God
40
What are nihilistic/cotard delusions?
False belief that one does not exist or has died
41
What are bizarre delusions?
Beliefs that are clearly impossible
| Not understood by peers and don't derive from life experiences
42
What is a delusion of reference?
Insignificant events/objects have great personal significance
43
What are delusions of control? What else can they be called?
External forces controlling oneself
| Passivity
44
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
```
45
What do second person auditory hallucinations indicate?
Psychotic depression
46
What do third person auditory hallucinations indicate?
Schizophrenia
47
How can we assess attention and concentration (cognition)?
```
Serial sevens (count down from 100 in sevens)
Digit span (give number sequence - ask to recall)
```
48
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
```
49
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
```
50
How many points are in the Addenbrookes Cognitive Examination?
100
51
How many points are in the Montreal Cognitive Assessment?
30
52
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
53
What is anautognosia?
Absence of awareness of ones own symptoms
54
What is dysautoagnosia?
Absence of attribution of symptoms to an appropriate mental disorder
55
How is early morning wakening described?
Waking >= 2 hours before expected/normal time
56
What is stupor?
Absence of relational functions
57
What is anhedonia?
Loss of enjoyment/pleasure
58
What is appearance and behaviour like in depression?
```
Reduced facial expression
'Furrowed' brown
Reduced eye contact
Limited gesturing
Difficult rapport
```
59
What is speech like in depression?
Reduced rate, volume, intonation
Lowered pitch
Increased speech latency
Limited content (short, brief answers)
60
What is a patient's mood like in depression?
'Flat'
61
What is a patient's affect like in depression?
Depressed
Reduced range
Limited reactivity:
- Doesn't respond/react to changes in subject/context/emotion
62
How is thought form affected in depressive moods?
Flow of thought:
- Slow and pondering
- Might be absent
63
How is thought content affected in depressive moods?
```
Negative, self-accusatory, guilt
Delusions may occur:
- Guilt
- Poverty
- Nihilism
- Hypochondriasis
```
64
What other symptoms tend to be presence alongside paranoia in psychosis?
Persecutory ideas/delusions
Altered perceptions
Lost insight
65
What types of auditory hallucinations can be present in depressive states?
2nd person and derogatory
66
What cognitive deficits are typically present in depressive states?
Working memory
Attention
Planning
67
How is insight affected in depression?
Typically preserved
68
In what conditions is insight often absent?
Schizophrenia
| Mania
69
What do patients experiencing depression often attribute their symptoms to?
Sins
Physical illness
Personal failing and weakness
70
What is the lifetime prevalence of depression?
14-18% in lifetime
71
How many cases of depression become chronic?
20%
72
How does DSM-5 classify depressive disorders?
Major Depressive Disorder
| Persistent Depressive Disorder
73
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
```
74
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
75
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
76
What are general criteria for depression?
Depressive episode lasting >= 2 weeks
| No hypomanic/manic symptoms at any point
77
What are the core features of depression (criterion B)?
At least 2 of the 3 following present:
1. Depressed mood:
- To an abnormal degree
- Present for most of day; almost every day
- Largely uninfluenced by circumstances
- Sustained for at least 2 weeks
2. Loss of interest/pleasure in normally fun activities
3. Decreased energy or increased fatiguability
78
The following are additional features of depression (criterion C):
1. Loss of self-confidence/esteem
2. Unreasonable feelings of self-reproach/excessive guilt
3. Recurrent thoughts of death/suicide or suicidal behaviour
4. Diminished ability to think/concentrare
5. Change in psychomotor activity
6. Sleep disturbance
7. Change in appetite (weight change)
At least 4
79
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
80
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
81
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
82
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
83
What do the following define:
1. Mood reactivity
2. 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
84
What is Cotard's Syndrome?
A type of psychotic depression
85
What are the features of Cotard's Syndrome?
Often nihilistic delusions
86
In what populations is Cotard's Syndrome more common?
Elderly
87
What is the median number of lifetime episodes in major depressive disorder?
4
88
What is the mean age of onset of major depressive disorder?
27 years
89
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)
90
How does DSM-V classify Bipolar disorders?
Bipolar:
- I
- II
Cyclothymic disorder
91
How does ICD-10 classify Bipolar disorders?
Hypomania
Mania with psychotic features
Mania without psychotic features
92
How is Bipolar I defined by DSM-V?
Has to meet criteria for mania
| Represents 'classic' form of manic-depressive psychosis
93
How is Bipolar II defined by DSM-V?
Current/past hypomania AND current/past depression
| No mania
94
What is the most common kind of Bipolar disorder (in terms of DSM-V classification)?
Bipolar II
95
What is Bipolar II.5 in terms of DSM-V?
Depressions superimposed on cyclothymic temperament
96
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
97
What is Bipolar III?
'Psuedo-unipolar'
| Hypomania ONLY after use of antidepressants for depression
98
What is Bipolar IV?
Depressions arising from a hyperthymic temperament
99
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
100
How does ICD-10 describe a hypomanic episode?
1. Mood is elevated/irritable
- To an abnormal degree
- Sustained for >=4 consecutive days
2. >=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
101
How does ICD-10 describe a manic episode?
1. Mood predominantly elevated/expansive/irritable:
- Definitely abnormal
- Prominent change sustained for >=1 week
- Or prominent change requiring hospital admission
2. >=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
102
What is F30.1?
Mania without psychotic symptoms
Perceptual disorders may occur:
- Subacute hyperacusis
- Appreciations of colours as very vivid
103
What is F30.2?
Mania with psychotic symptoms
104
What delusions or hallucinations must not occur in F30.2?
Those listed as Typical Schizophrenic:
- No bizarre delusions
- No 3rd person/running commentary hallucinations
105
What are the commonest delusions in mania with psychotic symptoms?
Grandiose
Self-referential
Erotic
Persecutory
106
When does bipolar disorder tend to onset?
Late teens/early 20s
107
If there is a family history of bipolar disorder, how does this affect onset of bipolar disorder?
Earlier
| Precipitated by lower levels of stress
108
Bipolar disorder that onsets after 60 years of age is often associated with what?
Treatment resistance
Progressive decline in functioning
Underlying organic cause
109
What gene is associated with Schizophrenia?
DISC2
110
What genes are associated with Schizoaffective disorders?
NRG1
G72
G30
111
What gene is associated with bipolar disorder?
ANK3
112
What is the most common mood disturbance in bipolar disturbance?
Depression (30-50%)
113
What ICD-10 range defines eating disorders?
F50-F59
114
What is F50.0?
Anorexia nervosa
115
What is F50.1?
Atypical anorexia nervosa
116
What is F50.2?
Bulimia nervosa
117
What are the four features of anorexia nervosa?
1. Weight loss (lack of weight gain in kids):
- Weight =<15% below normal for age and height
2. Weight loss in self-induced by fatty-food avoidance
3. Self-perception of being too fat (intrusive dread of fatness)
4. Widespread endocrine disorder:
- Involves hypothalamic-pituitary-gonadal axis
- Amenorrhoea in females (vaginal bleed while on HRT/COC)
- Loss of libido and potency in males
118
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
```
119
On recovery of pre-pubertal anorexia nervosa, what can occur?
Puberty usually completed normally
| Menarche is late
120
What are the DSM-V subtypes of anorexia nervosa?
Restricting
| Binge-eating/Purging
121
What are the four ICD-10 criteria for Bulimia Nervosa?
1. Recurrent overeating:
- >=2 times a week over >=3 months
- Lots of food in a short period of time#2.
2. Preoccupation with eating and cravings
3. 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)
4. Self-perception of being too fat
122
In terms of DSM-V, how many associated features must occur alongside binge episodes to diagnose a binge eating disorder?
>=3
123
What are some high risk indicative behavioural features for anorexia?
Feeding problems
Reduced BMI
Social difficulties
124
What are some high risk indicative psychobiological features for anorexia?
Reduced reward and increased threat
Sensitivity
Social cognition problems
Cognitive rigidity
125
What are some prodromal features of anorexia?
```
Coping:
- Avoidance
- Perfectionism
Compulsivity
Anxiety
```
126
What can indicate a severe enduring anorexia?
```
Social isolation
Impaired physical and mental QoL
Habits not goal-directed
Threat sensitivity
Reduced social cognition
```
127
What are some high risk indications for bulimia?
Robust feeding
Increased BMI
Increased reward sensitivity
Reduced response inhibition for food
128
What is the Standardised Mortality Ratio?
Ratio between number of deaths in a study population and the number of deaths that would be expected?
129
What is the Standardised Mortality Ratio for anorexia?
5.86
130
What is the Standardised Mortality Ratio for bulimia?
1.93
131
What causes refeeding syndrome?
Depletion of already inadequate stores of nutrients:
- Magnesium
- Potassium
- Phosphate
132
What is a low-moderate risk BMI?
17.5-16
133
What is a moderate risk BMI?
16-15
134
What is a high risk BMI?
14.9-13
135
What is a very high risk BMI?
<13
136
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
137
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
138
How does the Adults with Incapacity Act define an adult?
Aged >=16 year
139
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
140
What is Part 5 of the Adults with Incapacity Act?
Medical treatment
141
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
142
What does Section 47 prohibit?
Use of force unless immediately necessary and only for as long as is necessary
143
What article of the European Convention on Human Rights protects against arbitrary detention?
Article 5
144
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
145
Who can authorise Emergency Detention under the Mental Health Act?
```
Any doctor
(Preferably under guidance by a mental health officer)
```
146
How long can a person be detained under an Emergency Detention under the Mental Health Act?
72 hours maximum
147
Does Emergency Detention under the Mental Health Act allowed the patient to be treated against their will?
No
148
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
149
Who can authorise Short-Term Detention under the Mental Health Act?
Recommended by a psychiatrist and agreed by a mental health officer
150
How long can a person be detained under Short-Term Detention under the Mental Health Act?
28 days
151
Does Short-Term Detention under the Mental Health Act allowed the patient to be treated against their will?
Yes
152
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
153
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)
154
Who is allowed to object to anything under the Compulsory Treatment Order?
The patient
The patient's named person
The patient's primary carer
155
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
156
How long can a Compulsory Treatment Order last?
6 months initially
Can be extended for another 6 months
Then for another 12 months
157
Under what age does a person categorically have no consent?
If =<12 years
158
When might children younger than 16 have capacity?
They understand nature/purpose/consequences of intervention
| They understand consequences of not having treatment
159
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.
160
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
161
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
162
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
163
What antidepressants are deemed NA-selective?
Maprotiline
Protriptyline
Nortriptyline
164
What antidepressants are deemed non-selective?
Amitriptyline and Imipramine (1:1 ratio)
| Clomipramine
165
What antidepressants are deemed serotonin-selective?
```
Venlafaxine
Paroxetine
Sertraline
Fluoxetine
Citalopram
```
166
What class of drugs do Phenelzine, Isocarboxazid and Tranylcypromine belong to?
MAOI
167
What type of drug is Moclobemide?
Reversible Inhibitor of MonoAmine oxidase A (RIMA)
168
Give some examples of TCAs
```
Amitriptyline
Clomipramine
Imipramine
Nortriptyline
Dosulepin
```
169
Give some examples of SSRIs
```
Fluoxetine
Paroxetine
(Es)Citalopram
Sertraline
Fluvoxamine
```
170
Give some examples of SNRIs
Venlafaxine
| Duloxetine
171
What type of drug is Reboxetine?
NARI
172
What type of drug is Mirtazapine?
An atypical antidepressant with NA and specific serotenergic activity (NASSA)
173
What systems function to mediate seeking and approach behaviours (including pleasure)?
Ascending DA systems (mesolimbic/cortical)
| Ventral striatum
174
What is the dorsal striatum important for?
Movement
175
What is the amygdala important for?
Conditioning and learning
176
What is the function of the anterior cingulate?
Attention
Conflict
Response selection
177
What part of the brain is responsible for relative reward preference and rule learning?
Orbitofrontal cortex
178
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
```
179
What do MAOIs prevent?
The action of monoamine oxidase which breaks down:
- DA
- NA
- Serotonin
180
How do TCA work?
Act at presynaptic membrane to prevent serotonin and NA reuptake
181
In dopamine transmission, how is dopamine produced?
Tyrosine -> Levodopa -> DA
182
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
183
What effect do cocaine, GBR 12935, WIN 35,428 and RTI-121 have on the DA transporter?
Bind to receptor and inhibit DA reuptake
184
How is NA produced in a noradrenergic neurone?
Tyrosine -> L-DOPA -> DA (cytoplasm) -> DA (vesicle) -> NA
185
How does amphetamine affect the NA transporter (NET)?
Substrate
Reverses direction of neurotransmitter
Increases synaptic NA
186
What drugs inhibit the NA transporter?
Cocaine
Nisoxetine
Reboxetine
187
How is serotonin produced in a serotonergic neurone?
Tryptophan -> 5-Hydroxytrytophan -> Serotonin
188
How does amphetamine and MDMA affect the serotonin transporter?
Substrates
| Competitive reuptake inhibiton
189
What drugs inhibit the serotonin transporter?
Cocaine
Fluoxetine
Paroxetine
Sertraline
190
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
191
What enzyme converts tryptophan to 5-hydroxytryptophan?
Tryptophan hydroxylase
192
What enzyme converts 5-hydroxytryptophan to serotonin?
Aromatic-L-amino acid decarboxylase
193
What serotonin receptors are targeted by anti-depressants?
```
5-HT1a
5-HT2a
5-HT2b
5-HT2c
5-HT3
5-HT6
5-HT7
```
194
What drugs target 5-HT1b and 5-HT1d?
Migraine medications (eg. Triptans)
195
What serotonin receptor is targeted by anti-emetics?
5-HT3
196
What serotonin receptor has GI pro-kinetic effects and what is it used to treat?
5-HT4
| IBS and chronic constipation
197
On what receptor do fluoxetine and paroxetine at on?
5-HT2 (a-c)
198
On what receptors does Amitroptyline act on?
5-HT6
| 5-HT7
199
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
200
What circuits are indicated in SSRI use?
Limbic-cortical
201
What type of receptors are 5-HT1a receptors?
Inhibitory autoreceptors
202
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
203
What does chronic occupancy of the 5-HT1a receptor cause?
Desensitise it
Return to normal firing
Facilitates serotenergic transmission in presence of reuptake blockade
204
What is wrong with the serotenergic system in depression?
Dysregulation in transmission
| Serotonin is not low
205
Why are SSRIs typically first line?
Almost all can be started at a therapeutic dose
Usually good tolerance
Relatively safe in overdose
206
Why do SSRIs interact with other drugs?
Inhibit CYP450
207
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)
208
What drugs can cause reversal of an SSRI?
5-HT2 antagonists
| Partial 5-HT1a agonists (eg. Trazodone)
209
When might an SSRI be avoided?
Agitated depression
Intolerable GI effects
On warfarin (SSRIs can potentiate bleeding)
If on AEDs
210
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)
211
What drug for depression may be preferred in breastfeeding? (This is also the second choice SSRI in all with depression)
Sertraline
212
What is the typical dosing regime for fluoxetine?
20mg/day PO initially
Increased after 3-4 weeks if necessary
Max 60mg/day PO
213
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
214
What monitoring may be needed in high does TCA therapy and why?
ECG
| QT lengthening
215
What are the side effects of TCAs?
```
Constipation
Dry mouth
Blurred vision
Effects on cardiac function
Postural hypotension:
- Failure of peripheral orthostatic reflexes
```
216
What does MAO A metabolise?
NA
5-HT
Tyramine
217
What does MAO B metabolise?
DA
Tyramine
Phenylethylamine
218
When are MAOI used?
3rd or 4th line
| Often in atypical depression
219
What are side effects of MAOI therapy?
Flushing
Headache
Hypertension
CVA (rarely)
220
Why do MAOIs cause their side effects?
Tyramine is usually inactivated in the gut
| Since it remains active, NA is released
221
What can cause hypersensitive crises with MAOI therapy?
```
Tyramine-containing foods:
- Cheese
- Yoghurts
- Meat
- Alcohol
Drugs:
- Sympathomimetics (OTC cold remedies)
- Pethidine
```
222
How can the side effects of MAOIs be treated?
Alpha-blockade:
- Phentolamine
- Chlorpromazine
223
What side effects can some antidepressants (eg. Paroxetine) cause?
Extrapyramidal (due to effects on DA):
- Tremor
- Dystonia
- Akathisia
- Tardive dyskinesia
224
Give an example of an antipsychotic that may be an antidepressant at a low dose.
Flupentixol
225
What drug acts as a benzodiazepine receptor inverse agonist on the GABAa receptor complex?
FG-7142
226
What drug acts as a benzodiazepine receptor antagonist on the GABAa receptor complex?
Flumazenil
227
What drug acts as a benzodiazepine receptor agonist on the GABAa receptor complex?
Diazepam
228
When is a benzodiazepine receptor antagonist used?
Reversal of sedative effects benzodiazepine
OR
Treatment of benzodiazepine overdose
229
What effect does Picrotoxin have on the GABAa receptor?
Binds to the picrotoxin site:
- Channel blocker
- Stimulant and convulsant effects
230
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
231
What type of receptor is GABAa?
Ligand-gate ion channel
232
What drugs act as GABAa receptor agonists?
Ethanol
Benzodiazepines
Propofol
Anaesthetics
233
What drug acts as a GABAa receptor antagonist?
Flumazenil
234
What type of receptor is GABAb?
GPCR
235
What drugs act as GABAb receptor agonists?
Baclofen
| Propofol
236
What anticonvulsants act as mood stabilisers?
Carbamazepine
Valproate
Lamotrigine
237
What second generation antipsychotics can be used as mood stabilisers?
Olanzapine
Risperidone
Aripiprazole
Quetiapine
238
What other drugs can be used as mood stabiliers?
```
Lithium carbonate (citrate)
Nimodipine (calcium channel blocker)
```
239
How does lamotrigine work?
Blocking sodium channels
Doesn't work directly via GABA:
- Reduces excitability and cell firing
240
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
```
241
How do true/1st generation antipsychotics work?
Related to D2 receptor affinity
242
What circuit results in the desired effect of true/1st generation antipsychotics?
DA blockade in the mesolimbic circuits
243
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
244
What are the three mechanisms of action of 2nd generation antipsychotics?
1. Increased D2 receptor-binding affinity:
- Increased antipsychotic effectiveness
2. Increased 5-HT2c and a receptor-binding affinities:
- Increased antipsychotic efficacy
3. Increased 5-HT1a binding affinity:
- Reduced antipsychotic efficacy
245
What does structural imagine in bipolar disorder show?
Reduced grey matter volume in Brodmann Area 24 (anterior cingulate gyrus)
246
What does functional imaging in bipolar disorder show?
```
Increased metabolism in amygdala:
- Correlates with outcome
Reduced metabolism:
- OfC
- Medial ventral pfC
```
