Mood guidelines

Question 1

Limitations of clinical trials

Answer 1

1. Many of the studies funded by pharmaceutical companies that manufactured the medication under investigation.
   (designed to maximise the likelihood of identifying a favourable effect)
2. some studies are not reported because they
   are small and others because they have a negative outcome (failed trials). Data from such
   studies is often not made available
3. degree to which patients in clinical trials
   are representative of the population being treated is debatable with, for instance, many trials in
   depression excluding patients who are experiencing suicidal thoughts (a relatively common
   symptom in severe depressive disorders)
4. Clinical trials of psychotherapies ->potential biases including lack of blinding and
   expectation effects amongst both therapists and patients, psychotherapies
   are complex, multi-component interventions, and contrary to the logic of the randomised
   controlled trial (RCT), patients’ experience of and active participation in psychotherapy
   systematically influences the content of the intervention they receive.(RCTs are not optimal methodologies for validating psychotherapies,)

it must be remembered that RCTs and their meta-analyses are of variable
quality and validity.

Question 2

Methodological considerations in bipolar trials

Answer 2

1. Medication confounds
   - Recruitment-> on existing medications (unknown types, amount)

• Withdrawal
  Existing medication is withdrawn, usually within 5 half-lives of the medication, probably leading to
  discontinuation symptoms in a percentage of patients.
  Withdrawal symptoms are likely to be better treated with, for example, sedative and anticholinergic antipsychotics than by placebo, giving an immediate advantage to
  these drugs.
  Rapid withdrawal could also increase the risk of switching and exaggerate the effects of the added agent or, alternatively, mask the difference between the investigational drug and placebo.

2. Diagnostic inconsistency
   Trials contain varying percentages of patients with rapid cycling bipolar disorder who are usually
   not analysed separately.
   Some trials exclude patients with mixed features while others include them.
3. Selection, enrichment and drop-outs
   Selection
   Participant selection can be distorted by the pressure to enrol subjects leading to sub-optimal diagnostic accuracy and the inclusion of patients with illness severity less than the minimum
   designated.
   In some medication trials, the participants are offered financial inducements, usually to offset ‘out
   of pocket’ costs, but with the potential for distortions in the subjective reports of symptoms and
   disability.
   Participants who volunteer for medication trials often have “treatment resistant” illness and are therefore very willing to keep trying new treatments. It is known that some participants will enter
   multiple successive trials.
   Patients entering maintenance studies are often highly selected to be those who have tolerated,
   responded to and stabilised on a medication (enrichment).
4. Drop-outs
   Most trials in mania and depression report high dropout rates, usually within the first ten weeks
   (e.g. 50% dropout*), and
   There is usually further drop-out during a variable period of stabilisation that follows acute
   treatment

Question 3

Social construct of psychiatric diagnoses reference

Answer 3

There is growing consensus that psychiatric diagnoses are akin to social constructs (Insel, 2014; Zachar and Kendler, 2007).

the optimal classification of disorders must await a quantum leap in our understanding of the aetiology and pathophysiology of abnormal behaviour.
RANZCP mood guidelines

Question 4

Brief psychoeducation for mood disorders origin and development

Answer 4

The origins and development of mood disorders (however described) is definitively not known,
but it is certainly multi-factorial and the clinical expression is likely determined through a
combination of genetic predisposition, psychological vulnerabilities and life stressors. Interplay
of factors within these domains is thought to eventuate in brain/mind dysfunction. This
dysfunction is sometimes observable in neural changes, and is experienced subjectively as
distress that can manifest as overt behavioural change. Together these abnormalities result
in clinical signs and symptoms, which are grouped into syndromes and termed mood
disorders.

Question 5

What is PMDD and why does it now exist

Answer 5

Disruptive Mood Dysregulation Disorder (DMDD) is a new category included in DSM-5 to describe children who have persistent
irritability. Children with these symptom patterns are often found to go onto develop MDD, which is why this has been included within
depressive disorders. Previously, such children may have been diagnosed with paediatric bipolar disorder, which is conceptualised
as a more episodic illness and therefore a diagnosis of bipolar disorder is no longer appropriate in these cases. Part of the reason for
developing a diagnosis of DMDD is to stem the over-diagnosis of paediatric BD. However, this category remains contentious because of
its high comorbidity with other childhood disorders, and the potential risk of further over pathologising healthy children. It is best seen as
a category that enables further research on the natural history and best management of such presentations.

Question 6

BD1 overview
Episodes
Depression: duration, severity
Mania/Hypomania: duration, severity
Possible psychosis

Answer 6

BD I 
Mania +/–
hypomania
\+/–
depression

2Weeks
Marked
Impairment

Mania 7days
most of the
day nearly
every day or
hospitalisation

Marked
impairment
(Mania only)

Yes

Question 7

BD II overview
Episodes
Depression: duration, severity
Mania/Hypomania: duration, severity
Possible psychosis

Answer 7

Hypomania
+Depression

2Weeks
Marked
Impairment

Hypomania
4 consecutive
days, present
most of the
day nearly
every day.

No marked
impairment
in hypomania, impairment in
depression

Question 8

Cyclothymia
Episodes
Depression: duration, severity
Mania/Hypomania: duration, severity
Possible psychosis

Answer 8

Subthresholdc
hypomania +
subthreshold
depression

2 years with
no more than
two months
symptomfree

Clinically
significant
impairment

2years with
no more than
two months
symptom-free

Clinically
significant
impairment

No psychosis

Question 9

Depression
Episodes
Depression: duration, severity
Mania/Hypomania: duration, severity
Possible psychosis

Answer 9

Depression 
2Weeks 
Marked
Impairment
N/A 
N/A 
Yes

Question 10

PDD
Episodes
Depression: duration, severity
Mania/Hypomania: duration, severity
Possible psychosis

Answer 10

Depression 
2Weeks 
Clinically
significant
impairment

N/A
N/A
No

Question 11

DMDD
Episodes
Depression: duration, severity
Mania/Hypomania: duration, severity
Possible psychosis

Answer 11

Chronic
irritability
and temper
outbursts

> 12mths
with no more
than 3mths
symptomfree

≥3 Temper
outbursts
per week.

Present in
≥2 settings

N/A
N/A
No

Question 12

Episodes
Depression: duration, severity
Mania/Hypomania: duration, severity
Possible psychosis

Answer 12

Depression

Final week
before
menses to
a few days
after.

Causes
distress or
interference
with
functioning

N/A
N/A
No

Question 13

Mood disorders specifiers

Answer 13

Illness pattern:
single, recurrent, rapid cycling, seasonal

Severity:
mild, moderate, severe

Remission status:
partial, full

Onset:
early, late, peripartum

Clinical features:
anxious distress (mild, mod, mod-severe, severe), mixed features, melancholic, atypical, catatonic, psychotic (mood congruent, mood incongruent)

Question 14

MDD epidemiology, illness characteristics, treatment responsiveness

Answer 14

1. 1 in 10 patients in primary care present with depressive symptoms.
   Lifetime risk of depression is 15% and 12month prevalence is 4.1%.
   Depression is twice as common in females than males.
2. Mean age of diagnosis onset is 27years, but 40% have first episode by the
   age of 20years.
   At least 80% of those affected by depression will experience at least two episodes of illness (recurrence) in their lifetime.
3. 54% of individuals recover within 6months, 70% within one year.
   12–15% fail to recover and develop an unremitting chronic illness

Question 15

Bipolar 1 epidemiology, illness characteristics, treatment responsiveness

Answer 15

1. Lifetime prevalence is 0.6%.
   Affects both genders equally.
2. Mean age of diagnosis is late 20s
   Mean age of onset is late teens.
   The ratio of manic episodes to depressive episodes is 1:3.
   Nearly half of BD I patients experience a recurrence within 2years.
   Confers a significant risk of suicide (up to 30–60 times more than in
   general population)f
   especially during depression or with mixed features
   and a rapid cycling pattern
3. Age of onset and depressive burden appears to be predictive of future
   prognosis.
   Classic BD I patients are likely to respond better to lithium than to other
   medications.
   Lithium also protects against suicide

Question 16

Bipolar II epidemiology, illness characteristics, treatment responsiveness

Answer 16

1. Lifetime prevalence is 0.4% (Lower than BD I).
   More common in females than males
2. Median age of onset is 29years (later than BD I).
   Risk of suicide is as high as BD I with approximately 30% reporting a
   history of suicide attempts.

Question 17

Features that may distinguish bipolar and unipolar depression

FH, illness onset, onset/offset, comorbidity, duration of episodes, number of prior, mood symptoms, psychomotor sx, sleep disturbances, appetite changes, other sx

Answer 17

Bipolar:
More likely FH, alcohol/substance use
Early onset 20-25y
Abrupt onset/offset
ADHD comorbidity
<6 months duration
Multiple prior depressive episodes
Lability of mood/manic episodes
Psychomotor retardation
Hypersomnia/increased daytime napping
Hyperphagia
Other ‘atypical’ depressive symptoms such
as hypersomnia, hyperphagia, ‘leaden
paralysis’
Somatic complaints
Psychotic features and/or pathological guilt

Unipolar:
FH bipolar, alcohol and substance less likely
Late onset
More gradual onset
ADHD less common co-morbidity
>6 months episodes
Fewer prior episodes
Depressed mood/low energy
Psychomotor retardation less likely
Initial insomnia/reduced sleep
Appetite/weight loss
Somatic complaints

Question 18

Differential diagnoses of mood disorders

Answer 18

1. Other depressive and bipolar disorders
2. History of elated, excited, or irritable
   mood of any duration + increased levels of energy, family history
   of mania.
3. Adjustment disorder with depressed mood
4. Anxiety
5. Substance misuse, personality disorders, general medical disorders (hypothyroidism, sleep apnea)
6. Psychosis

Question 19

Overview BPSL treatments

Answer 19

1. Biological
   AD, AP, MS, ECT, TMS

2. Psychological
Brief CBT
F CBT
IPT
Mindfullness
ACT
Scehma therapy

3. Social
Family psychoeducation
Famil/friends
Formal support groups
Community groups
Caregivers
Employment
Housing

4. Lifestyle
Exercise
Diet
Smoking cessation
Alcohol cessation
Ceasing drugs
Managing substance misuse
Sleep

Question 20

Why formulation is important in relation to diagnosis

Answer 20

Formulation
builds on diagnosis, which has reliability but lacks the validity of formulation because the
latter contextualises the problems of the individual and provides a richer understanding as
to why he or she is unwell now. Formulation is also necessary because both treatments and diagnoses have been derived from studies of groups whereas management of mood
disorders is an individual (personalised) endeavour; therefore it is important to understand
the person in the context of their unique circumstances

Recognition of reslience and strengths

Question 21

Strengthening resilience in mood disorders

Answer 21

resilience to mood disorders can be strengthened biologically e.g.,
using lithium as a neuroprotective agent (Soeiro-de-Souza et al., 2012), psychologically
e.g., teaching cognitive reappraisal skills (Troy et al., 2010), socially e.g., improving social
support (Pietrzak et al., 2009), and through lifestyle change e.g., building exercise habits
(Hare et al., 2014)

Question 22

Definition of a clinical response

Answer 22

A clinical response is defined as a significant reduction in signs/symptoms
and is normally quantified as a 50% reduction in the total score on a standardised
rating scale, such as the Hamilton Depression Rating Scale (HAM-D)

Question 23

Three stages of illness

Answer 23

1. Acute phase
   Response to treatment initial aim
2. Continuation
   amelioration of symptoms continues, and the goal of treatment shifts to remission – formally defined by a cut-off score of less than 5
   on the HAM-D (Hamilton, 1960), or equivalent on the Montgomery-Asberg Depression
   Rating Scale (MADRS)
3. Recovery
   Following remission, treatment continues (continuation phase) until the patient regains
   complete functioning and returns to their premorbid state (recovery). At this stage, ongoing
   treatment may still be necessary (maintenance phase) to prevent recurrence and enhance
   resilience but the current episode has been treated.

Question 24

‘The person with the disorder’ reference

Answer 24

Unlike acute illnesses, where the clinician’s expert tools
are the primary lever for change, chronic illness management centres on the person with
the disorder.

Consequently, while “current classification systems and the treatment science
that depends on them emphasise objective features of the case, clinicians must be equally attentive to the patient’s subjective experience of the disorder and the management they
are receiving” (Berk et al., 2004).

Question 25

Example of effective online resource for mild/mod unipolar depression

Answer 25

MoodGYM (moodgym@anu.edu.au) as a CBT intervention to prevent and treat depression (and associated anxiety)

Question 26

Indications for psychiatric admission | - clinical presentation, co-morbidities, psychosocial variables, treatment variables

Answer 26

Clinical presentation: Severe depression with significant disability 1a. Suicidal ideation with seemingly imminent risk 1b. Medical risk (i.e., inadequate fluid intake)^ Mania 2a. Likelihood of escalating manic symptoms/early warning signs of imminent manic episode 2b. Significant impulsivity or reckless disinhibition in context of mania Insight is severely limited to the extent that outpatient treatment is not possible Significant psychotic symptoms Co-morbidities: Medical illness that influences course and treatment of mood disorder Alcohol and other substance misuse (particularly psychostimulants, cannabis, hallucinogens, benzodiazepines) Psychosocial variables: Lack of significant social supports (especially recent loss of supports) Stressful home environment Treatment variables: Inability to engage in community based care Failure to respond to community based care Initiation of complex treatments (e.g. Electroconvulsive therapy [ECT])

Question 27

Stepwise management of MDD

Answer 27

Goal: complete remission with functional recovery + development of resilience Step 0: Taper and cease any agents that can potentially lower mood Institute sleep hygein Implement appropriate lifestyle change- smoking, exercise, diet, substances Address substance misuse if relevant ->if insufficient Step 1: a) Generic psychosocial: psychoeducation (family, friends, caregivers), low intensity interventions (internet), formal support groups, community groups, employment, housing b) Formulation-based intervention -> psychological= CBTm IPT, ACT, mindfullness- based -> pharmacological= 1st line SSRIS, NaSSAs, NDRIs, SNRIs, NARIs, melatonin agonist, serotonin modulator 2nd line TCA, MOAIs ->If insufficient Step 2: Combine pharm + psych +dose of AD Augment antiD meds with lithium/antipsychotic Combine AD rTMS -> if insuffiencient Step 3: ECT

Question 28

Psychotherapy for depression acute phase

Answer 28

``` CBT IPT Non-directive supportive Behavioural activation Self-control therapy Short-term psychodynamic ```

Question 29

Psychotherapy for depression maintenance/relapse

Answer 29

CBT IPT MBCT

Question 30

Effect sizes for psychotherapies relative to antidepressant medication.

Answer 30

There is consensus that CBT is as effective as antidepressant medication for depression of mild-moderate severity (Lampe et al., 2013). metaanalysis of 10 relevant studies, which found the effect size of psychotherapy compared with pill placebo to be d=0.25 (NNT=7.14), which is comparable to the effects of antidepressant versus pill placebo (Cuijpers et al., 2014b).

Question 31

Common psychotherapies for treatment of major depressive disorder (CBT, IPT, ACT, MBCT)

Answer 31

1. CBT Cognitive-behavioural therapy (CBT) aims to modify dysfunctional cognitions and related behaviours that are presumed to maintain depression. Amongst evidence-based psychological therapies, CBT is the most widely researched treatment for depression, and it is recommended by all international guidelines 2. IPT Interpersonal psychotherapy (IPT) is a brief structured approach that addresses interpersonal issues and role transitions. It has Level I evidence for the treatment of major depression. IPT has Level 1 evidence for both acute depression and depression maintenance/ relapse. 3. MBCT and ACT Recently developed structured therapies, such as mindfulness-based cognitive therapy (MBCT) and acceptance and commitment therapy (ACT) have not been evaluated as thoroughly as CBT and IPT, but appear to be effective in reducing depressive symptoms and in preventing relapse of depression (specificity for subtype and/or severity of depression remains unclear) MBCT may be better for patients prone to worry and ACT may be best for patients needing to accept and adjust to persisting problems.

Question 32

Features of depressive disorder that may suggest more likely to respond to pharmacotherapy vs less likely to respond to pharmacotherapy as monotherapy

Answer 32

+likelihood previous response, the presence of atypical features, melancholic features, psychomotor retardation or psychotic features, and/or a family history of response to treatment less likely Significant dysfunctional premorbid personality factors (including child abuse history) (Nanni et al., 2012) and psychosocial precipitating factors

Question 33

Important side effects for SSRIs

Answer 33

hyponatraemia and osteoporosis, especially in the elderly, and a small risk of prolonged bleeding. Treatment with SSRIs during pregnancy has been associated with a small increased risk of foetal cardiac abnormalities (paroxetine) and potentially fatal pulmonary hypertension in the newborn and a neonatal withdrawal syndrome that can result in seizures has been identified

Question 34

Clinical considerations- SSRI

Answer 34

SSRIs are suitable first-line and are generally better tolerated than other classes of antidepressants but can cause emotional blunting. Sexual dysfunction and gastrointestinal symptoms are common. Many SSRIs (especially fluoxetine and paroxetine) cause significant CYP450 inhibition and care is needed when coprescribed with other medications. Paroxetine can cause withdrawal agitation.

Question 35

Clinical considerations- NARI

Answer 35

Reboxetine is suitable first-line. Common side effects include insomnia, fatigue, nausea, dry mouth and constipation.

Question 36

Clinical consideration-NaSSA

Answer 36

Mirtazapine is a suitable first-line option, but is associated with increased appetite, weight gain, somnolence, dry mouth and constipation. The last 3 side effects are also common with mianserin.

Question 37

Clinical considerations- melatonergic agonist

Answer 37

(agomelatine) | Common side effects include sedation and dizziness. Risk of hepatotoxicity.

Question 38

Clinical considerations-NDRI

Answer 38

(bupropion) | Common side effects include dry mouth, nausea and insomnia.

Question 39

Clinical considerations- SNRI

Answer 39

SNRIs appear to be more effective than SSRIs in treating severe depressive symptoms (HAM-D⩾25) and melancholia. In some cases, adverse effects may limit SNRIs to second-line treatment. However, if depression is severe (i.e. HAM-D>25), then SNRIs are a suitable first-line option. Headache, sexual dysfunction, sweating and gastrointestinal symptoms are common with venlafaxine. Can also cause withdrawal agitation.

Question 40

Clinical considerations- SM

Answer 40

(vortioxetine) Vortioxetine appears to have a particularly significant beneficial effect upon cognitive function in the treatment of depression. However the evidence requires further replication. Nausea, vomiting and diarrhoea are the major adverse effects

Question 41

Clinical considerations- TCA

Answer 41

In comparison to SSRIs, TCAs have a greater side effect burden (anticholinergic and CNS) and toxicity in overdose and therefore, are considered second-line. However, TCAs (especially those that have both noradrenergic and serotonergic activity such as amitriptyline and clomipramine) may be more effective compared to other antidepressants in treating severe depressive symptoms (HAM-D⩾25), in particular patients with melancholia and those hospitalised due to severe depression.

Question 42

Clinical considerations- MAOI

Answer 42

Efficacious antidepressants but not recommended first-line due to risk of hypertensive crisis if necessary dietary and drug interaction restrictions are not adhered to.

Question 43

Remission rates for antidepressant therapy- STAR*D study

Answer 43

The STAR*D study. (Rush et al., 2006) showed that after four successive trials of antidepressants a cumulative remission rate of 67% was reached, though it may require 2–3 antidepressant trials before complete remission is reached. Even with switching to an alternative medication or adding an augmenting agent, only 30% of depressed patients achieve a partial response or remain non-responsive (refractory). These patients require a more extensive re-evaluation of both the diagnosis and perpetuating factors, or are candidates for physical therapies such as ECT.

Question 44

First- and second-line indications for ECT.

Answer 44

``` First-line treatment Severe melancholic depression, especially when the patient is refusing to eat/drink High risk of suicide High levels of distress Psychotic depression or catatonia Previous response, patient choice ``` Second-line treatment Patients who have not responded to several trials of medication, including for example TCAs, MAOIs.

Question 45

Relapse rates for ECT

Answer 45

relapse rates within six months have been shown to be over 50% despite maintenance pharmacotherapy. Therefore in some cases maintenance ECT may be necessary

Question 46

rTMS overview

Answer 46

Mon-Friday treatment 30-45mins, 4-6 weeks No cognitive side effects, interactions, no anaesthesia repeated short bursts of high frequency stimulation (~10Hz) to the left dorsolateral prefrontal cortex (DLPFC). Patients with non-psychotic depression may be treated with rTMS once they have failed one or more trials of standard antidepressant medications and psychological therapies SE: headache and scalp discomfort

Question 47

Transcranial direct current stimulation

Answer 47

tDCS involves the application of a weak electrical current through an anode and cathode to subtly modify brain activity. Initial research suggests that tDCS can modify mood in depressed patients, although it is unclear at this stage whether these effects are clinically relevant. Antidepressant effects of tDCS have been supported in recent larger studies (Brunoni et al., 2013; Loo et al., 2012) and a meta-analysis (Shiozawa et al., 2014), but another recent meta-analysis found no difference between active and sham tDCS on clinically relevant endpoints, such as response and remission rates (Berlim et al., 2013). Definitive recommendations await the outcomes of large multi-site trials of tDCS that are currently underway.

Question 48

Magnetic seizure therapy

Answer 48

MST involves the induction of a seizure in a procedure similar to that undertaken with ECT (Fitzgerald et al., 2013a; Lisanby et al., 2001). However, instead of inducing a seizure with an electrical current, the MST seizure is produced using a high intensity transcranial magnetic stimulation device, which instigates the seizure via high frequency rTMS pulses. Initial data suggest that MST might have efficacy similar to ECT without equivalent cognitive side-effects (Kayser et al., 2011), but only limited evaluation of this technique has occurred to date.

Question 49

Deep brain stimulation

Answer 49

DBS is a procedure which involves the implantation of a small series of stimulating electrodes into the brain connected to a pacemaker type pulse generator which is placed below the clavicle in the chest. DBS is used extensively for patients with advanced Parkinson’s disease and a number of other neurological conditions Mixed evidence Serious and uncommon surgical complications

Question 50

Vagus nerve stimulation

Answer 50

Vagus nerve stimulation involves the surgical implantation of a pulse generator, similar to a pacemaker, in the chest wall that is connected to stimulating electrodes attached to the vagus nerve in the neck. The main existing indication for VNS is in the treatment of refractory epilepsy. A small series of studies has evaluated whether VNS has antidepressant effects (Nemeroff et al., 2006), and it appears to produce some antidepressant response but this emerges slowly and only in a minority of patients.

Question 51

Problematic issues with complementary therapy studies

Answer 51

marked variability in active | ingredient between brands, reflective of lower regulatory requirements (

Question 52

Should patient use of complementary therapies be respected?

Answer 52

if complementary therapies provide subjective benefit to patients, are affordable, are free of serious adverse effects, and do not prevent use of more proven conventional treatments, then the use of such therapies by patients should be respected. the sense of active coping and empowerment from using complementary therapies may enhance their sense of wellbeing and control, producing psychologically meaningful effects for them

Question 53

Healthy lifestyle management

Answer 53

1. Diet meta-analysis ->high adherence to a Mediterranean diet, also a very healthful dietary pattern, is associated with a 30% reduced risk for depression 2. Physical activity/exercise Meta-analysis effective intervention in depression (Stathopoulou et al., 2006) Augmentation strategy for depression 3. Smoking meta-analysis showed that smoking cessation is associated with reduced depression, anxiety, and stress and improved positive mood and quality of life compared with continuing to smoke 4. Omega-3 PUFAs 5. Sleep robust evidence for causal (often bidirectional) links between sleep and negative mood

Question 54

PREDIMED study

Answer 54

In the PREDIMED study, individuals at increased risk for cardiovascular events were randomised to a Mediterranean diet supplemented with either extra-virgin olive oil (EVOO) or mixed nuts, with a low-fat control diet. Although not statistically powered to assess prevention of depression, the results demonstrated a strong trend to a reduced risk for incident depression for those randomised to a Mediterranean diet with nuts, and this protective effect was particularly evident in those with type 2 diabetes (Sanchez-Villegas et al., 2013)

Question 55

biological mechanisms underlying the antidepressant effects of Omega-3 PUFAs

Answer 55

regulation of neurotransmitters serotonin and dopamine; mood stabilization via arachidonic acid cascade; anti-inflammatory and anti-oxidant effects; and positive actions on neuroplasticity and neurogenesis->similar to those of standard medications (e.g. antidepressants) and should be considered for use in patients for whom other treatment options are not acceptable. + adjunctive treatment.

Question 56

Managing partial or no treatment response

Answer 56

Clinical management 1. Review diagnosis 2. Re-assess co-morbidities 3. Review adherence and dose 4. Seek second opinion Therapeutic strategies 1. Increase dose 2. Augment/combine 3. Switch/substitute

Question 57

Results of antidepressant efficacy trials for response and remission

Answer 57

response rates of 60–70% but the rate of remission is much lower at 30–40% (Nierenberg et al., 2007). As a rule of thumb, only 1/3 of patients will remit with initial antidepressant treatment

Question 58

Reasons for poor response related to diagnosis

Answer 58

1. patient may have developed new symptoms, 2. the depression may be more complex than originally thought, or 3. an alternative diagnosis better explains the patient’s symptoms

Question 59

% of patients initially diagnosed with unipolar | depression will subsequently experience hypomania/mania in the course of their illness,

Answer 59

10%

Question 60

Switching strategies

Answer 60

(i) overlap-> always medicated, switch quick-> +SE and interactions (ii) taper or stop/start-> for partial, to help retain any benefit, +SE/interactions (can identify) (iii) washout-> cleanest, +worsening as unmedicated. When not responded.

Question 61

Augmenting with lithium

Answer 61

Level 1 evidence recommended that lithium be administered once daily at an oral dose that achieves trough plasma levels (0.5mmol/L to 0.8mmol/l) (Berghofer et al., 2006; Malhi et al., 2011). If there is no response to lithium within 7–10days, alternative strategies should be considered

Question 62

Predictors of response to lithium

Answer 62

recurrent major depression with more than | 3 recurrences and a family history in first degree relatives of bipolar or unipolar depression

Question 63

Augmenting with SGA

Answer 63

Placebo-controlled studies have found that aripiprazole, olanzapine, quetiapine and risperidone can be effective as augmentation agents. Once a stable response with augmentation has been achieved the gradual withdrawal of the augmenting second generation antipsychotic (SGA) agent should be considered.

Question 64

Factors increasing the risk of acute relapse in depression.

Answer 64

``` 1. Concurrent factors Gender (female) Life events/social stress Comorbid medical illness Poor compliance Persistent insomnia Personality Substance use Stress Poor supports Unemployment ``` ``` 2. Depressive features Severity of depression Duration of episode Presence of psychosis Residual symptoms Treatment resistance ```

Question 65

Lithium in maintenance phase depression

Answer 65

lithium monotherapy is an effective alternative maintenance treatment option (Cipriani et al., 2006) and may be considered if antidepressants cannot be tolerated (e.g., due to sexual dysfunction). Multiple trials over time have established the effectiveness of lithium monotherapy in the prevention of depressive relapse as confirmed by meta-analyses (Souza and Goodwin, 1991), with recommended levels typically at the lower end of the therapeutic range (Malhi et al., 2011; Schou, 1989).

Question 66

Maintenance treatment of MDD

Answer 66

1. Patients with depression should be monitored regularly beyond the acute phase of treatment to ensure complete remission of symptoms and full functional recovery. 2. MBCT or CBT should be offered as a relapse prevention intervention, particularly amongst patients with recurrent depressive episodes. EBR I 3. Once a satisfactory therapeutic response has been achieved, antidepressant dosage should remain the same during continuation and maintenance phases of treatment. EBR I 4. Maintenance antidepressant treatment should be continued for at least six months and up to one year.

Question 67

Cholinergic-rebound phenomena

Answer 67

Flu-like illness, myalgia, abdominal cramps

Question 68

Management of AD withdrawal

Answer 68

1. more frequent visits should be scheduled to ensure adequate monitoring and detection of early signs of depression recurrence. 2. Patients should be informed as to the potential symptoms that might emerge. 3. Family members or carers may also need to be engaged in this process and, 4. it would generally be prudent to avoid tapering off medications when patients are concurrently negotiating life events.

Question 69

Goal of management of mania

Answer 69

Treat the symptoms of mania and manage any associated behavioural and cognitive disturbance. Options for treatment: Acute symptoms of mania-> Antimanic agent Behavioural disturbance-> short term benzo, antipsychotic Cognitive disturbance-> Antipsychotic ECT-> consider if severe or high risk

Question 70

Stepwise pharmacological management of mania

Answer 70

1. Step 0 Taper and cease agents with mood-elevating properties (antidepressants and stimulants) Reduce stimulation, lower activity level, restore sleep cycle Maintain a structured routine and delay individual from making important decision -> if insufficient 2. Step 1 -->Commence antimanic agent (lithium SR 450mg/IR 500mg nocte or Valp 500mg BD, non-teratG if pregnant Olanz, risperidone, quetiapine, asenapine OR intramuscular haloperidol, olanzapine statim)-> with or without benzo/antipsychotic. If oral medications cannot be used after 2–3 injections of short acting intramuscular antipsychotics, zuclopenthixol acetate 50–100 mg may be used intramuscularly to provide parenteral medication without the need for frequent injections -->psychosis in 60%, second gen AP preferred to first gen 3. Step 2 (1 insufficient) -->two drug combination li + valproate, Li or oval + second gen AP, paliperidone, carbamazepine, ECT 4. Step 3 (2 ineffective) --> li + carbamazepine, valp + carb, clozapine, consider augmentation with tamoxifen/medroxyprogesterone

Question 71

Barriers to skill development targets of structured psychotherapy for mani

Answer 71

cognitive, emotional and behavioural dysregulation

Question 72

Psychological therapy in acute mania setting

Answer 72

Supportive psychotherapy, including psychoeducation, engage for future psychological therapy, collaborative, normalising, involvement of family Setting boundaries, limits, establish therapeutic relationship

Question 73

Treatment non-response- mania

Answer 73

1. Review diagnosis-> assess symptoms through self report, observation and corroboration from family. Consider rapid cycling or mixed features 2. Review investigations-> repeat FBC, UEG, LFTs, TFTs, neuroimaging, UDS 3. Address adherence to treatment-> med administration and levels + other strategies 4. Change medication-> prior to changing maximise doses of existing agents 5. Combination therapy-> higher discontinuation rates 6. ECT-> highly effective in refractory mania (level 2)

Question 74

Strategies to manage non-adherence- mania

Answer 74

1. careful supervision of medication administration, use of dosette devices and improved routines for medication use (for example linking consumption to another regular life event) 2. olanzapine wafers, risperidone quicklets, haloperidol and chlorpromazine syrups and asenapine wafers 3. depot antipsychotic medications, such as risperidone injection, olanzapine pamoate monohydrate, haloperidol decanoate, zuclopenthixol decanoate, flupenthixol decanoate, fluphenazine decanoate and paliperidone palmitate,

Question 75

Is risperidone/paliperidone depot useful in acute mania

Answer 75

not really- slow to achieve adequate bioavailability | Paliperidon slow to become efficacious

Question 76

Management of bipolar depression

Answer 76

1. Pharmacological: -> monotherapy: quetiapine, lurasidone, olanzapine (least favoured-> SE), lithium, lamotrigine, valproate ->combination: SGA's + MSA or AD. Caution Valproate in women CBA and woth lamotrigine Avoid combining AD with lamotrigine. Specific- Olanzapine and Fluoxetine 2. Psychological: -> adjunctive structured psychological interventions should be offered to help stabilise depressive episodes -> CBT, IPSRT, FFT 3. Physical -> ECT,

Question 77

Potentially complex issues in treating bipolar depression

Answer 77

treatment emergent affective switching (TEAS) into mania or hypomania, possible cycle acceleration, and the precipitation of mixed symptoms.

Question 78

Should AD be prescribed in treatment of BP1 depression

Answer 78

GENERAL CONSIDERATIONS 1. The use of antidepressants in the treatment of bipolar disorder should be overseen by a psychiatrist where possible. 2. The clinical risks versus benefits of antidepressants in treating bipolar depression should be determined on an individual basis. TREATMENT 1. Antidepressant monotherapy should be avoided in the treatment of bipolar depression with two or more coterminous manic symptoms. 2. Antidepressant monotherapy should be avoided for the treatment of an acute bipolar depressive episode that features psychomotor agitation or in the context of rapid cycling. 3. Antidepressant monotherapy should be avoided in Bipolar I disorder. TREATMENT EMERGENT AFFECTIVE SWITCH (TEAS) 1. Upon commencing antidepressants, patients with bipolar disorder should be closely monitored for symptoms of mania, and if these emerge antidepressant therapy should be discontinued. 2. Antidepressant therapy should be avoided in bipolar disorder patients with a history of rapid cycling and/or a high level of mood instability. 3. Antidepressant therapy should be avoided during ‘mixed states’ (mania with depressive features or depression with manic features). 4. The prescription of antidepressants should take into account any past history of a treatment emergent affective switch (TEAS).

Question 79

Pharmacological strategies for treatment of depressive episodes in bipolar II depression

Answer 79

the treatment of bipolar I depression is extrapolated to the treatment of bipolar II depression. However key differences regarding the evidence as compared with bipolar I depression are that antidepressants may be used as monotherapy noting that the evidence is modest at best, and that benefits are most likely early in the course of illness. quetiapine and lamotrigine are the most favoured respectively in clinical practice.

Question 80

Considerations prior to commencing AD in BPAD

Answer 80

mixed states, substance induced states, akathisia and adjustment disorders should be excluded. Patients and carers must be clearly informed of the risk of elevated states being induced with antidepressant therapy

Question 81

Rates of affective switching with AD type

Answer 81

TCAs (7–11%) and venlafaxine (13–15%) are associated with a higher risk of inducing mania compared with SSRIs (fluoxetine seems to have less risk) and bupropion

Question 82

STEP-BD trial

Answer 82

Miklowitz et al., 2007 Level II evidence for the efficacy of adjunctive psychological intervention when commenced during acute bipolar depression. Up to 30 sessions of Cognitive-Behavioural Therapy (CBT), Interpersonal and Social Rhythm Therapy (IPSRT) or Family-Focused Therapy (FFT were compared against a minimal psychological intervention of 3 sessions of ‘collaborative care’ for patients recruited in an acute depressive episode and continuing on pharmacotherapy The structured, intensive psychotherapies were associated with more frequent (and rapid) recovery from depression and better psychosocial functioning than collaborative care: year end recovery rates were 64.4% compared to 51.5%, and in any given month of the 12-month follow-up, patients in the intensive interventions were 1.6 times more likely to be clinically well. No differences were found between the three specific psychological therapies, so the evidence supports psychological intervention generally without specifying which type (see below).

Question 83

Psychotherapy for depressive phase and for maintenance phase of Bipolar Disorder.

Answer 83

Evidence-based psychological treatments Depression symptoms* & Relapse prevention 1. Psychological treatments as a set (individual, group, family) Level I Level I 2. Cognitive Behavioural Therapy (CBT) Level I Level I 3. Psychoeducation Level I Level I 4. Family-Focused Therapy (FFT) Level II Level II 5. Interpersonal and Social Rhythm Therapy (IPSRT) Level III Level III

Question 84

Define treatment resistant BP 1 depression

Answer 84

``` failure to reach remission with adequately dosed lithium (blood level 0.6–0.8 mMol/L) or to other adequate ongoing mood-stabilizing treatment, plus lamotrigine (50–200mg/day) or with full dose quetiapine (⩾ 600mg/day) as monotherapy. ```

Question 85

Pharmacological strategies to address non-response BP depression

Answer 85

Bipolar I depression. Quetiapine (or other atypical antipsychotic or mood stabilizer if preferred) alone → Quetiapine or Lithium + Lamotrigine (latter with care) or Olanzapine + Fluoxetine → Lithium or Quetiapine + SSRI or Bupropion → Pramipexole or Modafanil → Electroconvulsive therapy. Bipolar II depression. Similar to management of bipolar I depression but include irreversible monoamine inhibitors as options when combining Lithium or Quetiapine (or other atypical antipsychotic or mood stabilizer if preferred) with an antidepressant (with care if combining lithium with MAOI). Brain stimulation approaches. Very few studies have evaluated the use of rTMS treatment in homogeneous groups of patients with bipolar depression. However, many depressed patients with bipolar disorder have been included in trials of rTMS with no evidence that bipolar patients are less likely to respond to rTMS than patients with unipolar depression (Fitzgerald et al., 2013b), and overall, the rate of manic switch with rTMS treatment appears to be low. Physical treatments such as ECT, appropriately timed bright light therapy (particularly if a seasonal component is involved) (Poon et al., 2012), vagus nerve stimulation (Rizvi et al., 2011) and repeated transcranial magnetic stimulation (George, 2010) should all be reserved for specialist centres and patients need to be monitored medically and for the emergence of manic switches

Question 86

Adjunctive strategies BP depression

Answer 86

1. thyroid hormones (Bauer et al., 2005), glutamate antagonists (memantine/riluzole) (Owen, 2012), intravenous ketamine (Zarate et al., 2012), and modafinil/armodafinil (latter is the R-enantiomer of modafinil) (Calabrese et al., 2010)-> all experimental. 2. Omega-3 fatty acids, NAC

Question 87

Continuation therapy pharmacological options relating to polarity

Answer 87

Depression predominates: lithium or valproate in combination with olanzapine, quetiapine, lamotrigine or aripiprazole Monotherapy: mania predominates-> lithium and olanzapine depression-> lamotrigine equal-> quetiapine

Question 88

Phases of long-term treatment.

Answer 88

Acute (weeks, months)-> remission (continuation, up to 6 months)-> recovery (maintenance, review every 12 months)

Question 89

The principal aims of maintenance treatment

Answer 89

``` Maintaining mood stabilist Achieving complete functional recovery Providing long term prophylaxis Reducing attraction to the euphoria and enhanced abilities of past hypomanic states Building resilience and improving QoL ```

Question 90

Recurrence prophylaxis reassessment

Answer 90

``` efficacy number of relapses/recurrences predictability of episodes subsyndromal sx side effects and tolerability functioning and QOL on maintenance Severity of illness and impact of episodes on QoL ```

Question 91

Drug Maintenance therapy BPAD-> following reassessment of status at 6 months of relapse prophylaxis

Answer 91

1. Drug continuation if: multiple past, hasty unpredictable shifts, side effects tolerable and safe, monitoring in place, patient compliant, high risk 2. Drug tapering if: lower risk, intolerable or unsafe side effects 3. Drug switching if: intolerable side effects, continued moderate risk, loss of efficacy Monitor signs of recurrence-> reassess every 12 months-> efficay, subsyndroma sx, side effects and tolerability, level of functioning and QoL

Question 92

BALANCE Sudy

Answer 92

the BALANCE study (Geddes et al., 2010) ->demonstrated that lithium alone and in combination with valproate is effective in prophylaxis. Lithium is more effective alone than valproate alone, and carries the extra significant benefit of reducing suicidal behaviour and death by suicide.

Question 93

BALANCE Sudy

Answer 93

the BALANCE study (Geddes et al., 2010) ->demonstrated that lithium alone and in combination with valproate is effective in prophylaxis. Lithium is more effective alone than valproate alone, and carries the extra significant benefit of reducing suicidal behaviour and death by suicide.

Question 94

Valproate in maintenance-> evidence

Answer 94

Valproate is not formally approved for use as a maintenance agent and remarkably there are no RCTs that have demonstrated its efficacy in long-term prophylaxis. In comparison to lithium, it is less effective (Geddes et al., 2010) but does have modest efficacy in acute mania (Calabrese et al., 2005a; Macritchie et al., 2001; Tohen et al., 2003a). It is therefore often advocated in those patients that have a predominance of manic episodes.

Question 95

Novel agents used to stabilise circadian rhythm sin bipolar

Answer 95

agomelatine and ramelteon, that have an effect of stabilising circadian rhythms, could theoretically be used. Ramelteon has been used with some positive findings as an adjunctive agent to treat insomnia (McElroy et al., 2011; Norris et al., 2013) and agomelatine has had mixed findings for the treatment of bipolar depression (Calabrese et al., 2007; Fornaro et al., 2013; Yatham, 2015).

Question 96

Psychological treatment in long-term management of bipolar disorder

Answer 96

1. CBT Focuses on the reciprocal relationships between thinking, behaviour and emotions to decrease symptoms and relapse risk. 2. Psychoeducation Aims to assist people to become experts on managing their bipolar disorder, emphasising adherence to medication and stabilising moods. Psychoeducation is a descriptive term referring to providing information about the condition, but has been developed into manualised high intensity treatments by two groups of researchers (Bauer et al., 1998; Colom et al., 2003) and these formal interventions are the focus of the majority of the evidence base. 3. FFT Based on evidence that family stress and interactions moderate relapse, FFT aims to improve communication and problem-solving skills in the family. Although only one family member may have a diagnosis of bipolar disorder, the entire family is considered ‘the client’. 4. Interpersonal and social rhythm therapy An amalgamation of interpersonal therapy addressing losses, role conflicts and other interpersonal problems with behaviours aimed at stabilising circadian rhythms via stabilising social rhythms (e.g., fixing wake time across 7days of the week).

Question 97

Shared content elements of evidence-based psychological interventions for BPAD

Answer 97

Improve ability to recognise changes in mood and signs of prodromal periods, and to respond quickly and effectively (via pre-planning) to these prodromal symptoms Increase knowledge about and acceptance of BD, including acceptance of, and adherence to medication regimens Encourage daily monitoring of mood and sleep Improve interpersonal communication, particularly in the family Improve significant others’ understanding of BD, including ability to identify and productively respond to prodromal symptoms Re-engage with social, familial and occupational roles Improve stress response and emotion regulation skills, especially around goals and reward activation Proactively stabilise sleep/wake and other social rhythms Identify and critique maladaptive thoughts and beliefs, particularly in relation to the self and the disorder Reduce drug or alcohol misuse

Question 98

Carers and the care of individuals with bipolar disorder

Answer 98

1. acknowledge the impact of the illness upon the affected individual, their family, and other carers 2. carers form an integral part of the management team with their capacity to provide often-crucial additional information, and to assist in the implementation of interventions 3. acknowledge the impact of serious mental illness like bipolar disorder on carers, the level of stress that carers may experience and their heightened risk for the development of their own mental health problems such as anxiety or depression 4. issues surrounding carer involvement and confidentiality are often particularly sensitive where capacity to consent to treatment is impaired and involuntary treatment is required

Question 99

Persistent depressive disorder- treatments

Answer 99

A recent meta-analysis suggests that antidepressants are superior to placebo for the treatment of PDD, with SSRIs having better tolerability than TCAs. antidepressants for subthreshold depressive symptoms is not established CBT appears less effective than SSRIs, but the combination of therapies appears more effective than either alone Given the lack of clear efficacy of antidepressants in this group, psychosocial interventions should be encouraged prior to considering medications.

Question 100

Persistent depressive disorder- treatments

Answer 100

A recent meta-analysis suggests that antidepressants are superior to placebo for the treatment of PDD, with SSRIs having better tolerability than TCAs. antidepressants for subthreshold depressive symptoms is not established CBT appears less effective than SSRIs, but the combination of therapies appears more effective than either alone Given the lack of clear efficacy of antidepressants in this group, psychosocial interventions should be encouraged prior to considering medications.

Question 101

cyclothymia- sx and treatments

Answer 101

prolonged states (1year in children and adolescents, 2years in adults) during which periods of subsyndromal hypomania and depressive symptoms have been present for the majority of the time (>50%) and there has been no period of more than 2months when the individual has been symptom free. Where distress and dysfunction arising from cyclothymic disorder are mild, conservative non-pharmacological approaches alone should be trialled initially, more severe symptoms it is unclear if pharmacotherapy is useful augmented CBT was effective for depressive and hypomanic symptoms, compared with clinical management Family involvement important BPD- potential differential

Question 102

Depression Mixed features- treatment

Answer 102

For depressed patients with mixed features, taper and cease substances with a mood-elevating effect or those that may induce inter-episode switching (e.g., antidepressants, stimulants). Consider treating the patient with olanzapine (Level II) (Tohen et al., 2014), quetiapine, or valproate as monotherapy or in combination with an antidepressant, or valproate in combination with olanzapine (Level II) (Benazzi et al., 2009). Lamotrigine adjunctive to an antimanic agent may be a useful option for mixed states to treat depressive symptoms

Question 103

Dysphoric mania- treatment

Answer 103

antidepressants should be prescribed with care, as these may aggravate the mixed state or promote rapid cycling Second generation antipsychotic medications, in conjunction with a mood stabiliser (Muralidharan et al., 2013) are more effective than mood stabilisers alone and are recommended for use in dysphoric mania, with Level II evidence for asenapine olanzapine aripiprazole, ziprasidone and risperidone There is an absence of evidence regarding the use of quetiapine for the acute treatment of mixed states With regard to maintenance therapy, valproate appears to be more effective than lithium

Question 104

doubts about SAD as a distinct clinical entity

Answer 104

Evidence that SAD also responds to antidepressants (Lam et al., 2006) and CBT (Rohan et al., 2009), while nonseasonal depressions also respond to bright light (Golden et al., 2005) raises doubts about SAD as a distinct clinical entity

Question 105

doubts about SAD as a distinct clinical entity

Answer 105

Evidence that SAD also responds to antidepressants (Lam et al., 2006) and CBT (Rohan et al., 2009), while nonseasonal depressions also respond to bright light (Golden et al., 2005) raises doubts about SAD as a distinct clinical entity

Question 106

Management of mood disorders in the context of comorbidities- Depression and BPAD and w comorbid anxiety, substance use

Answer 106

1. Depression-> Agomelatine may be superior Exceptional cases AD with long term clonazepam 2. BPAD-> Achieve mood stabilisation CBT for bipolar disorder augmented with anxiety strategies may have the strongest evidence. Pregabalin, quetiapine, olanzapine, Valproate and lamotrigine Short term benzo's

Question 107

Comorbid substance use may be a consequence of

Answer 107

1. The underlying primary mood disorder, reflecting attempts to ‘self-medicate’ mood symptoms. However, eventually depressive symptoms may emerge because of the depressogenic effects of the substance or because the mood disorder has taken hold. In essence, there is a complex and interactive relationship between substance misuse (especially alcohol) and depressive symptoms. 2. The mood disorder being a psychiatric complication of substance use (e.g. euphoria during the initial phase of psychostimulant use followed by depression during the ‘crash’ phase). It is noteworthy that co-morbid alcohol and substance use disorders are associated with a worse course of bipolar disorder including more mood symptoms, recurrent mood episodes and decreased likelihood of recovery, more suicides, more hospitalisations and higher levels of aggressiveness (Suppes and Cosgrove, 2014

Question 108

Treatment of depression with comorbid substance use disorder

Answer 108

A meta-analysis of comorbid substance use disorder with major depression found depressive symptoms did not significantly improve with SSRI treatment, but other classes of antidepressants (notably TCAs) may have some efficacy venlafaxine has been shown to be ineffective in treating depressive symptoms comorbid with cannabis use, and may in fact be associated with greater cannabis use (Levin et al., 2013) NICOTINE-> bupropion or nortrptiline Hepatic impairment-> desvenlafaxine Stimulants-> caution serotonergic, SS

Question 109

Treatment of bipolar disorder with comorbid substance use disorder

Answer 109

Integrate CBT with group drug counselling | Use of valproate may help reduce alcohol consumption in some patients

Question 110

Summary of relationships of mood disorders and BPD. MDD vs BD vs BPD

Answer 110

1. Affective dysregulation MDD->Mood is depressed with varying severity vs Mood varies between depression, euphoria, or irritability (suggests mixed states) vs Mood often contains intense rage, with intermittent anxiety and depression. 2. Age of presentation-> Any age, but particularly early adulthood vs Late adolescence and young adulthood vs Early adolescence. 3. Illness trajectory-> Recurrence is common vs Onset: usually prominent affective signs and symptoms. Onset: usually behavioural and interpersonal difficulties. vs Course: Depressive and mixed episodes become more common with advancing age. Course: intensity of core features improves approaching the fourth decade. May then exhibit improved capacity to maintain close relationships, and improved affective regulation. 4. Depressive features-> Large range of affective features vs Features of melancholia, agitation, mixed affective episodes, all occur commonly. Intense guilt when depressed vs Shame, ‘a noxious sense of self’ (intense self-loathing and self-denigration). Prominent cognitive, selfdefeating core beliefs and projection. MDD may arise comorbidly. 5. Manic features-> Nil vs Hypomania is an essential clinical component. Irritable mood/affect is common but not always present vs Affective instability is key feature rather than prolonged shifts in mood and affect. Irritability is ubiquitous. 6. Impulsivity-> Low vs High, but fluctuates markedly with periods of mania vs High and persistent. Often a trait as well as state phenomenon. 7. Social cognition -> Good appreciation of the emotional states of others and meaning for them, when euthymic vs Good appreciation of the emotional states of others and meaning for them when euthymic vs Poor appreciation of the emotional states of others and meaning for them. Often respond to these distorted perceptions negatively (sometimes positively) and may use this to cope with internal emotional pain. 8. Psychosis-> May be present vs Present only in BD I vs Psychotic episodes may arise and periods are of brief duration (hours or days), paranoid in content, may include delusions and hallucinations. Occur at times of intense emotional stress. Dissociative phenomena may be misdiagnosed as psychosis. 9. Self/identity-> Mostly positive sense of self, except when severely depressed vs Mostly positive sense of self, except when severely depressed. Elevated sense of self importance and potency when hypomanic vs ‘Noxious sense of self’ with self-loathing, sometimes alternating with fragile self-grandiosity. 10. Relationship quality-> Relationships often suffer adversely from the disorder vs Relationships often suffer adversely from the disorder vs Relationship difficulties are a primary deficit in this disorder. Interpersonal chaos is common. Intense ambivalence and fear of abandonment are core problems. Improve with age 11. Family history-> Family history of mood disorder is common vs Family history of mood disorder is common vs Family history of mood disorder and/or personality disorder is common. 12. Childhood trauma-> common in all 13. Self harm-> intermittent vs intermittent vs frequent

Question 111

Management of BD with comorbid substance use

Answer 111

1. Prior to making a definitive diagnosis of a mood disorder and commencing antidepressant/mood stabiliser therapy, a proper assessment and diagnosis of substance use issues should be conducted and if possible effective treatment of a substance use disorder should be implemented. 2. In cases of comorbidity with substance dependence or severe substance use disorders, detoxification followed by relapse prevention measures should be implemented first. 3. When considering the use of TCAs in patients with major depression continuing to misuse substances, the potential benefits should be balanced against the risk of suicide. ``` 4. For patients with severe alcohol or other substance use disorders (DSM-5), detoxification should occur followed by relapse prevention measures integrated with CBT (Integrative Group Therapy – IGT) to maintain abstinence. ``` 5. Early intervention should be considered in patients with mild substance use disorders

Question 112

Pharmacotherapy BPD

Answer 112

Limited benefit atypical AP best established efficacy Atypical antipsychotics and mood stabilzers (including lithium, sodium valproate and lamotrigine) -> concurrent Bipolar Disorders, affective instability, impulsivity and aggression. Antidepressants and atypical antipsychotics have value when Borderline Personality Disorder is comorbid with Major Depressive Disorder.

Question 113

Differential for depressive sx and schizophrenia

Answer 113

1. rule out the presence of medical factors contributing to depressed mood (e.g., cardiovascular disorders or cancer); 2. second, the role of prescribed drugs, such as beta-blockers or the use of illicit substances, including alcohol; 3. third, the role of dopaminergic blockers in the development of dysphoric symptoms, given that antipsychotics block dopamine receptors with high potency potentially disrupting activity in reward related brain pathways, resulting in anhedonia or dysphoric symptoms. 4. negative symptoms of schizophrenia The presence of cognitive features of depression, such as guilt, hopelessness and suicidal thoughts, along with distinct sadness rather than blunting of affect are more suggestive of depression. 5. Post-psychotic depression -> depressive symptoms following the resolution of an acute psychotic episode. 6. stress-related reaction including symptoms of post-traumatic stress disorder or depression 7. Prodrome of psychotic relapse

Question 114

Management of emerging depression in schizophrenia

Answer 114

Consider differentials Emerging risks-> suicidality Any suggestion of emerging relapse should be treated with AP appropriately Additional support and monitoring Supporting psychotherapy-> address illness and lifestyle related stressors Review dose of ongoing AP-> possible dose reduction or switch to less potent DA blocker if considered to be aetiological factor Unclear role of AD

Question 115

Management of emerging depression in schizophrenia

Answer 115

Consider differentials Emerging risks-> suicidality Any suggestion of emerging relapse should be treated with AP appropriately Additional support and monitoring Supporting psychotherapy-> address illness and lifestyle related stressors Review dose of ongoing AP-> possible dose reduction or switch to less potent DA blocker if considered to be aetiological factor Unclear role of AD

Question 116

Bidirectional relationship with mood disorders and physical health

Answer 116

1. Depression can impede engagement in therapies for comorbid medical conditions thus worsening prognosis. 2. Medical comorbidities – particularly chronic pain – appear to reduce antidepressant efficacy 3. SSRIs are effective in ischemic heart disease and comorbid major depression-> more effective than psychological counselling alone 4. Vascular depression-> poorer antidepressant efficacy and tolerability 5. Citalopram high doses-> QTc 6. SSRI-> bleeding 7. High rates medical comorbidities: obesity, migraine, hypertension, hyperlipidaemia, asthma, diabetes, endocrine and metabolic syndromes. Less commonly reported conditions include thyroid and parathyroid disorders, liver disease, hepatitis C, HIV, peptic ulcer disease, pancreatitis, autoimmune disorders and renal impairment. 8. CVD-> lifestyle behaviours, medications, hyperphagia during depression, sedentary

Question 117

Management of mood disorders with comorbid medical illnesses

Answer 117

1. Newly diagnosed mood disorders patients should undergo medical evaluation to determine baseline comorbidities – such as: hypertension, obesity, diabetes, sleep apnoea, and thyroid, renal and liver dysfunction. 2. Illness-related behaviours and lifestyle risk factors should be identified and monitored during the management of mood disorders alongside appropriate counselling aimed at behaviour modification and prevention of medical comorbidity. 3. Tailored monitoring of medication related effects on medical health should be conducted routinely and include, monitoring of weight; lipids and blood sugars; blood pressure; thyroid, renal and liver function; white cell count; and menstrual function in women. Cardiac-> When treating mood disorders patients with cardiac problems second generation antidepressants should be given preference because of better overall tolerability and safer cardiac and anticholinergic side effect profiles Hepatic-> Desvenlafaxine should be given preference over venlafaxine when hepatic interactions are clinically relevant. Pain-> In the treatment of comorbid pain and depression tricyclic antidepressants should be given particular consideration*.

Question 118

Management of mood disorders with comorbid medical illnesses

Answer 118

1. Newly diagnosed mood disorders patients should undergo medical evaluation to determine baseline comorbidities – such as: hypertension, obesity, diabetes, sleep apnoea, and thyroid, renal and liver dysfunction. 2. Illness-related behaviours and lifestyle risk factors should be identified and monitored during the management of mood disorders alongside appropriate counselling aimed at behaviour modification and prevention of medical comorbidity. 3. Tailored monitoring of medication related effects on medical health should be conducted routinely and include, monitoring of weight; lipids and blood sugars; blood pressure; thyroid, renal and liver function; white cell count; and menstrual function in women. Cardiac-> When treating mood disorders patients with cardiac problems second generation antidepressants should be given preference because of better overall tolerability and safer cardiac and anticholinergic side effect profiles Hepatic-> Desvenlafaxine should be given preference over venlafaxine when hepatic interactions are clinically relevant. Pain-> In the treatment of comorbid pain and depression tricyclic antidepressants should be given particular consideration*.

Question 119

Risks vs benefits of medication in pregnancy

Answer 119

``` 1. To woman Nil meds: Persistent depression Distress Adverse effect on pregnancy outcome Taking medication: Maternal wellbeing ``` 2. Developing foetus Nil meds: no risk of harm from medication, Possible adverse impact on foetal development from exposure to maternal mental illness Taking medication: Possible reduced risk of effects of severe depression on foetal development, Risk of harm from exposing foetus to medication

Question 120

Risks vs benefits of medication in pregnancy

Answer 120

``` 1. To woman Nil meds: Persistent depression Distress Adverse effect on pregnancy outcome Taking medication: Maternal wellbeing ``` 2. Developing foetus Nil meds: no risk of harm from medication, Possible adverse impact on foetal development from exposure to maternal mental illness Taking medication: Possible reduced risk of effects of severe depression on foetal development, Risk of harm from exposing foetus to medication

Question 121

Management of major depressive disorder in children and adolescents

Answer 121

1. Assessment and treatment planning must go beyond the narrow diagnostic picture to explore family and social context, patient/family preference and potential barriers to engaging with treatment. 2. Optimal management of significant mood symptoms in young people requires specific experience and expertise with this population, and therefore consultation with a specialist child/adolescent/family service should be considered and sought if necessary. 3. Psychological interventions (particularly CBT or IPT) should be used first-line for the treatment of MDD in children and adolescents. 4. For moderate to severe MDD in children and adolescents who are not responsive to psychological intervention, short-term use of fluoxetine for acute symptom reduction may be trialled. 5. Children and adolescents prescribed antidepressants must be closely monitored for emergent suicidality, hostility, agitation, mania, and unusual changes in behaviour. 6. In cases where an antidepressant is used, continuation or commencement of psychological intervention should be considered for additional benefits on global functioning. 7. ECT should be available for the treatment of severe affective or psychotic illnesses and catatonia in children and adolescents, when pharmacological treatment is ineffective. 8. Assessment for ECT should include an adequate assessment by a child, adolescent and family service and an agreement by that service that ECT is indicated and consenting procedures must conform to the legislation requirements of the Mental Health Act in each jurisdiction

Question 122

Management of bipolar disorder in adolescents

Answer 122

1. Diagnosis of BD in adolescents should be based on satisfying criteria for Bipolar I Disorder – specifically there should be distinct and recognisable episodes of depression and mania. 2. Assessment and treatment planning must go beyond the narrow diagnostic picture to collaboratively explore family and social context, patient/family preference and potential barriers to engaging with treatment. 3. Optimal management of BD in adolescents requires specific experience and expertise with this population, therefore should involve a specialist adolescent/ family service. 4. Adolescents with bipolar I disorder should be offered psychosocial intervention with family involvement, and the costs/benefits of pharmacotherapy should be considered carefully. 5. Adjunctive psychosocial treatment should include psychoeducation for the family, skill development for the young person, and relapse prevention drills. 6. ECT should be available for the treatment of severe affective or psychotic illnesses and catatonia in children and adolescents, when pharmacological treatment is ineffective. 7. Assessment for ECT should include an adequate assessment by a child, adolescent and family service and an agreement by that service that ECT is indicated and consenting procedures must conform to the legislation requirements of the Mental Health Act in each jurisdiction.

Question 123

Pathophysiology of BD

Answer 123

The pathophysiology of bipolar disorder, or manic-depressive illness (MDI), has not been determined, and no objective biologic markers correspond definitively with the disease state. However, twin, family, and adoption studies all indicate that bipolar disorder has a significant genetic component. In fact, first-degree relatives of a person with bipolar disorder are approximately 7 times more likely to develop bipolar disorder than the rest of the population, and the heritability of bipolar I disorder (BPI) has recently been estimated at 0.73 1. The condition is likely to be caused by multiple different common disease alleles, each of which contributes a relatively low degree of risk on its own 2. Multiple biochemical pathways likely contribute to bipolar disorder 3. Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response may also contribute to the clinical picture of bipolar disorder. 4. White matter hyperintensities(WMH) are more common 5. decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has been associated with the regulation of emotions 6. Depression as a manifestation of lossess, mania serves as a defense against the feelings of depression 7. external stresses or the external pressures may serve to exacerbate some underlying genetic or biochemical predisposition

Question 124

Pathophysiology of BD

Answer 124

The pathophysiology of bipolar disorder, or manic-depressive illness (MDI), has not been determined, and no objective biologic markers correspond definitively with the disease state. However, twin, family, and adoption studies all indicate that bipolar disorder has a significant genetic component. In fact, first-degree relatives of a person with bipolar disorder are approximately 7 times more likely to develop bipolar disorder than the rest of the population, and the heritability of bipolar I disorder (BPI) has recently been estimated at 0.73 1. The condition is likely to be caused by multiple different common disease alleles, each of which contributes a relatively low degree of risk on its own 2. Multiple biochemical pathways likely contribute to bipolar disorder 3. Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response may also contribute to the clinical picture of bipolar disorder. 4. White matter hyperintensities(WMH) are more common 5. decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has been associated with the regulation of emotions 6. Depression as a manifestation of lossess, mania serves as a defense against the feelings of depression 7. external stresses or the external pressures may serve to exacerbate some underlying genetic or biochemical predisposition

Question 125

Important considerations in postnatal depression

Answer 125

1. Mother-infant dyad- attachment/quality of the mother-infant relationship and safety of the infant and woman's capacity to provide a safe and nurturing environment 2. Assessment of intimate relationship- DV may impact on safety issues 3. Psychosocial treatments, such as CBT, non-directive counselling and IPT 4. additional support to assist them in compensating for fatigue induced by sleep deprivation as a result of nursing the baby. The provision of both practical and emotional support is of critical importance 5. More severe- AD, consider breast feeding (avoid fluoxetine), considre impact on sedation

Question 126

Pregnancy planning for women with bipolar disorder.

Answer 126

1. careful risk-benefit analysis for remaining on mood stabilising medication needs to be done 2. sodium valproate can cause significant harm to the foetus, which has a foetal congenital abnormality rate ranging from 5 to 17% 3. risks of congenital abnormalities are lower for carbamazepine (3%) and lamotrigine (2%) 4. For women with severe bipolar disorder lithium appears to be the safest option amongst available mood stabilisers. 5. Women should have folate supplementation and an ultrasound to determine whether an abnormality is present (along with a plan as to what to do should an abnormality be found). Lithium can be safely reintroduced in the latter stages of the pregnancy in order to provide prophylaxis against relapse. Lithium management in the latter stages of pregnancy is more complex and requires careful monitoring and dose reduction prior to delivery to avoid exposing the foetus to toxic levels of lithium 6. Breastfeeding contraindicated with lithium, use SGA or anticonvulsant 7. SGAs can be used as alternative to MSA 8. Benzodiazepines, or a sedating antipsychotic can be used in the short term to assist in restoring a stable sleep–wake cycle (consider sedation, capacity to care/feed) 9. ensure adequate contraception and contraceptive advice is provided to the woman 10. If relapse, suggest treatment in specialised mother and baby unit