General Adult Psychiatry Flashcards
Comparing depot formulations which induces more EPSEs Haloperidol, Zuclopenthixol or Flupenthixol?
Zuclopenthixol - good symptom control but higher potency to cause EPSEs
Do depot antipsychotics have a higher risk of NMS?
No - the risk of tardive dyskinesia is also the same for oral preparations of the same drug
In the context of schizophrenia which antipsychotic drug has the best anti-suicide properties?
Clozapine - indirect evidence for SGAs but no direct longitudinal studies
D-cyloserine has been used as an add-on for the treatment of?
Schizophrenia/psychosis
it is a partial agonist at the glycine site of NMDA receptor and there is some evidence to suggest it can treat negative symptoms
Name some findings from the national epidemiological survey of alcohol and related conditions (NESARC) with respect to depression?
- Highest risk of depression is age > 30
- Mean number of episodes in patients with lifetime MDD is 5
- Longest duration was 24 weeks per episode
N.b studies have found the prevalence of depression is changing - point prevalence in NSEARC increased from 3.3% to 7% (lifetime prevalence 13%)
In what percentage does the diagnosis of depression eventually change (Kessing 2005)?
56%
- 16% to schizophrenia
- PD 9%
- Neurotic stress and somatoform disorders 8%
- Bipolar Disorders 8%
How long does depressive episode last treated vs untreated?
Untreated 6 - 13 months
Treated 3 months
What is the risk of recurrence in depression?
50% will have no future episodes
50% will have a recurrence < 5 years
If 2 episodes risk of recurrence is 70%
If 3 episodes risk of recurrence is 80-95%
For depression define response, recovery, relapse, remission and recurrence
Response is a decrease in symptoms from at least 50%
- partial response is a decrease from 26-49%
If no detectable symptoms and continue to do so after the natural period of a treated depressive episode (3 months) - HAMD < 7 this is termed remission
If this is maintained for 6 months - this is termed recovery
Return of symptoms within the 6 months is called a relapse
Return of symptoms after this period is a new episode and called recurrence
Do males or female relapse more for depression?
Females
For mixed depression and anxiety what do NICE advocate treating first?
Depression
When may SSRIs be continued for at least 2 years after the episode?
If > 2 prior episodes in recent past or if residual symptoms are present
In depression when lithium augmentation in combination with an anti-depressant is tried and a good response elicited how long should this be continued?
At least 6 months of both
What is NNT of anti-depressants for response/remission in short term trials (12-14 weeks)
Response 4-5
Remission 6-7
Briefly outline the stepped care approach to treatment by NICE?
Primary care and general hospitals - recognition for assessment and screening
Treatment of mild depression in primary care
- Self-guided CBT
- Watchful waiting
- Self-help
- Computerised CBT
- Exercise
- Brief psychological therapies
Treatment of moderate-severe depression
- Medication use
- Psychosocial support
- CBT - alone or in combination
Specialist treatment
- Medication
- Complex psychotherapies
- Combined treatments
Inpatient treatment
- Risk management
- ECT/combined treatments
For depression outline the acute, continuation and maintenance phases?
Acute - stabilisation of symptoms up to 3 months (aim for remission)
Continuation phase - 6-12 months (recovery begins at 6 months if symptom free). It covers the natural untreated course)
Maintenance phase - prevents recurrence - treatment dependent on risk factors and probability
Outline the levels in STARD
Level 1 - Citalopram encouraged to continue 12 weeks
Level 2 - if no remission at 12 weeks in level 1 randomised to the following based on preference to switch, augment or combine:
- Switch (Buproprion, Sertraline, Venlafaxine)
- Switch to CBT
- Augment Citalopram with (Bupropion, Buspirone)
- Combine Citalopram with CBT
Level 3 - if no remission at 12 weeks in level 2 randomised to:
- Switch to Mirtazapine, Nortriptyline
- Augment level 2with Lithium or thyroid
Level 4: no remission after 12 weeks in level choose to:
- Switch to Tranylcypromine or Nortryptyline
- Combine Mirtazapine with Venlafaxine
Name some pertinent findings from STARD?
Cumulative response was 67% after 4 steps
50% symptom free after 2 levels
Switch within and to different class anti-D from SSRI no difference statistically
No statistical differences between level 3 and level 4 treatments
Which anti-D classes and examples within class are most toxic in overdose?
From high to low mortality risk:
TCAs - dosulepsin and doxepin
Mirtazapine / Venlafaxine
SSRI - Citalopram
What are the 5As that can result in TRD?
Alcoholism
Adequate anti-D dose
Adherence
Axis 2 disorders
Alternate diagnosis
How does agomelatine work?
5HT2c antagonist - works as Serotonin works to drive GABAergic interneurons that tonically inhibit dopaminergic and noradrenergic circuits in the PFC
Agomelatine stops this inhibition
What does activated charcoal absorb poorly and effectively?
Effectively:
- TCAs
- Paracetamol
- Aspirin
- Theophylline
- Aspirin
- Barbiturates
Not effectively
- Lithium
- Alcohol
- Magnesium
- Potassium
- Sodium
- Acids
- Alkalis
Works well with non-polar poorly water soluble organic toxins
Contraindications for charcoal:
- Unprotected airway
- GI perf
- If endoscopy to be attempted
- If charcoal won’t absorb the item
Outline some considerations with St Johns wart?
Inducer of CYP450
- There is no identified therapeutic dose
- Similar AE to placebo in trials but interactions and can cause serotonin syndrome
- Cochrane evidence showed benefit for mild/moderate depression
Which condition is most associated with rapid cycling bipolar disorder?
Hypothyroidism
What is the prevalence of Bipolar Disorder as per the NCS-replication?
BD-1 1%
BD-2 1.1%
These are lifetime prevalences
The mean age of onset of BP-I was 18.2 whereas for BP-II tit was 20 years
What is the median time for treated mania to resolve?
4-5 weeks
Name some features in bipolar disorder that females are more likely to experience than men?
Mixed episodes, rapid cycling and depressive symptoms
Outline the ICD-11 & DSM-V criteria for mania
At least 1 week of:
- Elevated, euphoric or expansive mood AND increased activity or subjective energy
With “several (ICD-11)” or “3 or more (DSM-V)” additional features:
- Pressure of speech
- Flight of ideas
- Increased self-esteem or grandiosity
- Decreased need for sleep
- Distractibility
- Impulsive or reckless behaviour
- Rapid changes among different mood states
- Increased sexual drive, sociability or goal directed activity
What is mood destabilisation?
The long term phenomenon where anti-depressants cause more mood episodes over time than what would have occurred in the natural course
- N.b anti-depressants can induce switching and mood destabilisation or one or the other
RF for switch:
- FHx of BPAD
- Exposure to multiple anti-D trials
- Initial illness beginning in adolescence or young adulthood
- Previous anti-depressant induced mania
How many episodes a year constitutes rapid cycling?
> /= 4 a year
If >/= 4 a month ultra-rapid cyclin
If a patient has switches on >/= 4 days a week termed ultra-ultra rapid or ultradian rapid cycling
How does treating de novo mania vary to mania already on a mood stabiliser?
De novo:
- Stop anti-D if on one
- Initiate an antipsychotic with rapid acting anti-manic effect (preferable options include haloperidol, olanzapine, quetiapine or risperidone)
- Adjunctive benzodiazepine
If on a mood stabiliser:
- Increase the dose (check levels if Lithium)
-If optimising levels is ineffective then add haloperidol, olanzapine, quetiapine or risperidone
- If severely ill during pregnancy or severely ill and patient preference consider ECT
Outline preference options for bipolar depression?
Olanzapine + Fluoxetine
Quetiapine
Lamotrigine
Outline some guidance/options for managing maintenance in bipolar disorder?
Consider after a single manic episode and BD-II with severe functional impairment
1st line - Lithium (responders typically have euphoric mania, full remission, no comorbidity, no psychotic features, fewer liftime episodes, mania-depression-euthymia course)
Valproate - protects against manic and depressive
Olanzapine - prevents manic > depressive
Quetiapine - especially if effective in acute phase
Carbamazepine less effective than lithium
Lamotrigine - prevents against depressive > manic
How does DSM-V define personality disorders?
A) Enduring pattern of inner experience or behaviour that deviates markedly from socio-cultural expectation and manifests in changes in:
- Cognition
- Affectivity
- Impulsivity
- Interpersonal functioning
B) Pervasive and inflexible and is demonstrated across a range of situations
C) Significant distress/loss of functioning
D) Pattern can be traced back to early adulthood
E) Not explained by another medical disorder
F) Not explained by medication or substance misuse
Describe the ICD-11 personality disorder criteria?
An enduring disturbance in aspects of the functioning of the self (self-worth, identity, view of self, capacity for self-direction) and/or interpersonal functioning (ability to form and maintain close and mutually satisfying relationships, ability to see others perspectives and ability to manage conflict)
Disturbance over an extended time > 2 years
The disturbance manifests in patterns of cognition, emotional expression, emotional experience and behaviour that is maladaptive (poorly regulated an inflexible)
Shows in a range of personal and social settings (i.e not just one role/social experience) though a particular setting may evoke it and not others
Causes distress or impairment in functioning (personal, social, occupational or educational)
Not explained by other medical condition, medication or substance misuse
Not developmentally appropriate and not explained by politico-cultural context
What are the 5 trait specifiers in ICD-11?
- Dissociality
- Detachment
- Anakastia
- Disinhibition
- Negative affectivity
N.B borderline pattern has been kept as a specifier
In DSM-V which PD cannot be diagnosed pre 18?
Anti-social
If on tamoxifen which anti-depressant would be helpful as thought to be safe?
Venlafaxine
Which sedatives are thought to be safe in hepatic impairment?
Oxazepam
Lorazepam
Zopiclone
Temezepam
Outline the incidence/prevalence of schizophrenia?
Incidence estimated at 15.2/100,000 person years (Kirkbride 2012)
Prevalence 0.4%, for all psychotic disorders 0.63% (lifetime prevalence at age 43) - roughly consistent with 1% lifetime prevalence.
In SPMM 4.6/1,000 point prevalence noted
N.B the above refer to UK rates - internationally prevalence estimated at 0.33% and incidence 0.2/1,000 person years
Rates are higher in urban areas, migrant populations and developed countries
How do the Iowa 500 and Bon Hospital study counteract pessimistic claims about recovery in schizophrenia?
In Iowas 500 - 46% improve or recover over follow up (average of 35 years)
In Bonn Hospital Study - 22% had complete remission, 43% had remission of psychosis only (follow up of 22.4 years)
What is simple schizophrenia as described by Eugene Bleuler?
Insidious onset of social withdrawal with prominent negative features (relative absence of hallucinations, delusions and thought disorder)
Outline the positive symptoms detailed in the PANSS scale?
Delusions
Conceptual disorganisation
Hallucinations
Excitement
Grandiosity
Suspiciousness/persecution
Hostility
n.b. negative symptoms include:
- blunted affect
- emotional withdrawal
- difficulty in abstract thinking
- stereotyped thinking
- lack of spontaneity and flow of conversation
- poor rapport
- social withdrawal
What is the risk of schizophrenia if you have one 1st degree relative with the condition vs both parents?
12-15%
Both parents 40-50%
MZ concordance is 46%
Sexual side effects with SSRIs are associated with what receptor action
5-HT2A stimulation
- therefore drugs which poses 5HT stimulation with 5-HT2A antagonism have less sexual side effects - namely Mirtazapine
Why may the BDI be preferable to the MADRS or SCAN?
Patient reported and acceptable less skilled training required
What do the most severe cases of serotonin syndrome involve?
MAO-I + SSRI
What was drop out from treatment more commonly associated with in the STAR-D
Higher perceived MH functioning, less education, younger age
Interestingly experience with > 1 episode of depression was associated with less drop out
Broadly outline some obstetric complications associated with schizophrenia?
- Growth related events - low birth weight, small for gestational age
- Peri-natal risk factors - perinatal induced hypertension, hypoxic events
- Hypoxic events e.g. premature rupture of membranes
Lewis-Murray scale has been specifically designed to measure obstetric complications during childbirth (OR from various studies are too low to be significant)
Name 4 features of psychoeducation
Briefing patients about the illness
Problem solving training
Communication training
Self-assertiveness training
What is the NNT of family therapy in relapse prevention of Schizophrenia?
6
Who devised social skills training and what are the 3 forms?
Bellack and Mueser
- Basic model - complex social interactions are broken down into steps, the individual has corrective learning and practices through role playing
- Social problem-solving model - address difficulties in information processing that are assumed to cause problems in social impairment
- Cognitive remediation model - targeting fundamental cognitive impairments like attention or planning that will aid cognitive processes and will be applied in social environments
Name some psychosocial interventions for schizophrenia?
CBT-P
Vocational rehabilitation
Family therapy
Social skills training
What proportion of patients relapse
a) Within 1 year of FEP irrespective of antipsychotic treatment?
b) Within 1 year of FEP if on placebo > antipsychotics
c) Within 1 year following five or more prior episodes (irrespective of antipsychotics)
d) Within 1 year following five or more prior episodes (on placebo)
a) 27%
b) 61%
c) 48%
d) 87%
Name some brain regions associated with OCD?
OFC, cingulate gyrus, striatum (caudate nucleus, putamen), globus pallidus , thalamus
It is proposed that this neuronal loop is involved in the pathophysiology - indeed lesions in this area and surgical treatments that disrupt the loop (cingulotomy, anterior capsulotomy, sub-caudate tractotomy) can treat symptoms.
What is the difference between acute stress reaction vs acute stress disorder?
Reaction < 3 days
Disorder 3 days - 1 month
Over this period and need to screen for PTSD
For acute stress reaction symptoms should typically dimish within 48hrs after removal of the stressor
If stressor is ongoing the symptoms should be greatly reduced by 1 month
In OCD what percentage change in Y-BOCS is indicative of a treatment response?
Reduction of 25-35% of pre-treatment score
What proportion of patients with restless leg syndrome have periodic limb movements during the night?
80-90%
Periodic limb movements is seen in 1/4 of middle aged individuals
How does URGE outline the symptoms of restless leg?
Urge to move legs
Rest worsens urge to move
Getting up relieves symptoms
Evening or night worsens symptoms
Disorders that mimic RLS have been excluded
Supportive criteria:
- 1st degree relative
- Periodic limb movements occuring during the night
What is the treatment for restless legs syndrome?
- alpha 2 delta calcium channel ligands (Gabapentin, pregabalin, enarcarbil)
- Dopamine agonists (Pramipexole, Ropinrole, Rotigotine)
In narcolepsy type 1 (with cataplexy) which neuropeptide is low?
Hypocretin type - 1 (orexin)
Loss of these neurons leads to lack of suppression of REM promoting neurons AND inactivity of wakefulness promoting neurons
This then respectively activates pathways that inhibit motor activity (sleep paralysis and cataplexy) and loss of muscle tone (drop attacks)
Outline some REM related and non-REM related parainsomnias?
REM related - REM sleep behaviour disorder, recurrent isolated sleep paralysis, nightmare disorder
Non-REM related (arousal related) - sleepwalking, sleep terrors, sleep eating disorder, confusional arousals
Other para-insomnias include exploding head syndrome, nocturnal enuresis, sleep related hypnic hallucinations
In psychiatric outpatient samples what cluster of personality disorders is most common?
Cluster C - 22%
Cluster B - 13%
Cluster A - 6%
Any PD - 46%
Name some groups of patients that may require lower doses of Clozapine?
Non-smokers
Female patients
On CYP50 inhibitor (SSRI)
Elderly
Is risk of neutropenia related to Clozapine dose?
NO
Can Clozapine be used alongside carbamazepine?
NO - both can cause agranular cytosis
Why should patients who have agranular cytosis (ANC < 0.5) attributable to Clozapine not be re-challenged?
As the second reaction is often more severe and acute than the first
Which drugs have RCT evidence to treat Clozapine induced hyper-salivation?
Amisulpride and hyoscine hydrobromide
Which anti-depressants may be more effective for psychotic depression (combining with an antipsychotic)
TCAs
In ICD-11 what are the BMI categories for anorexia?
Significantly low 14 - 18.5
Dangerously low < 14
If an individual develops tardive dyskinesia on an antipsychotic which would be the most acceptable step?
Switch to an antipsychotic with a lower propensity to cause TD
What is a neurovegetative symptom?
Symptoms associated with poor functioning of the nervous system such as fatigue, sleeping problems or poor energy
What is the prevalence of bulimia in the general population?
0.5 - 1%
The average suicide rate in the UK for the…
a) General population
b) MH service users
a) 1 in 10,000
b) 1 in 1,0000
Name some anti-depressants that are safe and some that should be avoided in hepatic impairment?
Sertraline
Paroxetine
Citalopram
Vortioxetine
Avoid: TCAs and MAOI
Name some risk factors for Agranulocytosis and neutropenia on Clozapine?
Agranulocytosis:
- Asian
- Increasing age
Neutropenia
- African-caribbean
- Low age
- Low baseline neutrophil count
The suicide rate in epilepsy is BLANK compared to the general population?
3 x higher
The rate of non-compliance due to forgetting to take the medication is?
10%
Name some scales that assess medication compliance?
DAI - Drug attitude inventory (attitudes and beliefs about medication compliance)
MARS - medication adherence rating scale (frequency and consistency of medication taking and factors that may influence it)
How does anaemia present in anorexia?
Normocytic and normochromic, it may be masked by plasma depletion
Can be accompanied by thrombocytopenia
Anaemia occurs in 1/3 patients
When does rapid cycling tend to occur in BPAD?
Late in the illness course, in some individuals may resolve within 2 years (50%)
What are the psychiatric risks of the anti-retroviral drug Efavirenz?
Mania and completed suicide
In STAR*D how many people responded to the first phase of Citalopram?
30%
Asthenic personality disorder also refers to?
Dependent personality disorder (it is the older term)
The lifetime prevalence of suicide in Schizophrenia is?
5.6%
What is the standardised mortality ratio in Schizophrenia?
2.58
The SMR for Schizophrenia is rising - n.b standardised mortality rates are generally declining in most nations which suggests that individuals with Schizophrenia aren’t accessing life prolonging interventions
How did Olanzapine outperform other “atypicals” in the CAITE study?
Through less dropouts
Overall the CAITE study did not find significant differences between first and second generation antipsychotic drugs in terms of efficacy/cost
What are the minimum effective doses of the follwing antipsychotics according to the Maudsley Prescribing Guidelines?
1) Olanzapine
2) Risperidone
3) Haloperidol
4) Amisupride
5) Sulpride
6) Aripiprazole
7) Chlorpromazine
8) Trifluperizine
FEP dose presented first, then in relapse of multi-episode:
1) 5mg, 7.5mg
2) 2mg, 4mg
3) 2mg, 4mg
4) 300mg, 400mg
5) 400mg, 800mg
6) 10mg, 10ng
7) 200mg, 300mg
8) 10mg, 15mg
Generally FEP may respond to lower doses
No clear evidence if maintenance needs lower dose than acute episode
What did the CAITE data indicate with “stayers” or “switches” especially with Olanzapine
“Stayers” had preferable outcomes than “switchers”
Name some antipsychotics helpful for managing aggression?
Clozapine > Olanzapine > Haloperidol
What is deficit Schizophrenia?
- Two of a) Restricted affect b) diminished emotional range c) diminished social drive d) diminished sense purpose e) curbing of interest
- Two or more of the features must be present in the prior 12 months and alway present during periods of clinical stability (chronic psychotic states) and may or may not be present in acute transient psychotic disorganisation
- Two of the factors are idiopathic rather than due to anxiety/depression, drug effects, positive symptoms etc
- Patient meets DSM-V diagnosis for schizophrenia
How do primary and secondary negative symptoms differ
Primary - intrinsic to Schizophrenia
Secondary - result of positive symptoms, medication, affective changes, environmental situation etc
Which antipsychotic may be helpful for negative symptoms?
Amisulpride (as per Maudsley guidelines)
- Olanzapine has some evidence
Other drugs…
- Also add on D-cycloserine
- Glycine
- Selegine
What did the Intersept study show regarding effective antipsychotics for preventing suicide in schizophrenia or schizoaffective disorder?
Clozapine outperformed Olanzapine (HR 0.76)
n.b hazard ratio is relative risk for a hazard event
What is the minimum period that individuals should continue an antipsychotic for after
a) FEP
b) Multi-episodes
a) 1-2 years
b) 5 years if not indefinitely
Which antipsychotic drugs may be less sedating?
Aripiprazole, Amisulpride, Haloperidol
Should patients have a lower dose in the maintenance period?
Not necessarily - use the minimum effective dose, often this is the same dose as was reached to treat the acute episode
What is the advised quickest dose escalation frequency for HDAT?
Not more than weekly
How many haloperidol resistant patients responded with Clozapine during 6 weeks?
30% (vs. 4% of Chlorpromazine)
Meltzer concluded that 20% may also respond within 3 months and 10-20% within 6 months
The plasma therapeutic level of Clozapine?
Unclear but advised to aim for 350-450ng/ml
What adjuncts have been studied to augment Clozapine?
- Lamotrigine - RCT showed improvement with positive symptoms and general psychopathology
- Risperidone - evidence if Risperidone dose around 4.5mg/day and Clozapine 475mg/day
- Amisulpride/Sulpride - high D2 blockade (Clozapine not thought to act via this)
- Fluoxetine - ?by CYP inhibition
In CAITE phase 2 study what was compared?
Efficacy pathway - if discontinuation < 18 months due to non-response Clozapine vs other atypicals
- Clozapine time to discontinuation was 3 x longer than other atypicals (Olanzapine, Risperidone, Quetiapine or Ziprasidone)
- Median time to discontinuation for Clozapine was 10 months
Tolerance pathway if couldn’t tolerate the medication:
- Here Olanzapine, Risperidone, Quetiapine and Ziprasidone were compared
- Olanzapine and Risperidone moderately more effective than Quetiapine and Ziprasidone
Describe the treatment of schizoaffective disorders?
Mood stabiliser:
- Carbamazepine has good efficacy for depressive subtype
- Carbamazepine/Lithium equally effective for manic subtype
Antipsychotics - in combination or as own as mood stabilising effect
Anti-depressant guidance is the same as BPAD