Melancholic and Psychotic Depression – Review of Diagnosis and Management

MELANCHOLIC DEPRESSION - CLINICAL FEATURES

Melancholic depression is characterised by:

• Psychomotor disturbance
• Impaired cognitive functioning (frontal-subcortical circuits)
• Slowing of mental and motor activity
• Physical symptoms, e.g. constipation, menstrual irregularities, lowered BP
• Ruminations – themes of hopelessness, pessimism, self-accusation, self-derogation, feelings of inadequacy and of being a failure
• Periods of agitation
• More significant biological and genetic determinants than psychosocial
• Shows a minimal response to placebo
• Show a superior response to biological treatments such as broad-spectrum antidepressant medication and electroconvulsive therapy rather than psychotherapy.

In the DSM-5, melancholic depression is not a separate diagnosis and is accorded a specifier rather than a sub-type status.

However, treating melancholic depression like major depression without recognising the distinct clinical presentation can be associated with non-response to narrow-spectrum antidepressants (e.g. SSRIs) and poorer outcomes.

In a STAR*D study report (using DSM-IV criteria), 23.5% (n=2875)  of patients with melancholic features had higher severity scores, greater rates of previous suicide attempts and ratings of current suicidal risk, and more concurrent psychiatric comorbidity. They also had a 24.1% decrease in the relative chance of remission compared to patients with non-melancholic depression. [McGrath P et al., 2008]

Since psychomotor change is a key feature in melancholic depression, one of the early diagnostic tools developed was the CORE signs which assessed the following 18 items of psychomotor disturbance. [Parker G et al.,2013]

The CORE had two main limitations.

• Patients in remission or early stages of illness may not show significant psychomotor change.
• The patients studied for this scale were > 40 yrs of age.

Considering the above limitations, Parker G et al., 2017 developed the Sydney Melancholia Prototype Index (SMPI) to operationalise clinical diagnostic judgment for melancholic depression.

Red flags for melancholic depression

Melancholia is divided into functional and structural melancholia.

Collateral history is important in the diagnosis of melancholic and psychotic depression.

Family members often describe a significant change in behaviour, e.g. change in tone of voice, “he or she is just not the same”, “loss of light in their eyes”, changes in posture, speed of movement and speech, pacing behaviour, wringing hands, or umming and ahhing a lot when talking.

Impact of Melancholic Depression on the Brain:

• Repeated episodes of melancholic depression have been associated with decreased brain volume in the basal ganglia and hippocampus. [Hickie I et al., 2005]
• The decrease in brain volume may be related to the duration of untreated depression, and antidepressants may have a neuroprotective role. [Sheline Y et al., 2003]

CASE STUDIES

Below are two referrals from General Practitioners (GPs). Both patients had not responded to multiple antidepressants.

Both cases have several features of melancholic depression described above.

One can see commonalities in their presentation, with the first case being on the more severe end of the melancholic spectrum and the latter less severe.

Case 1:

Learning points:  Pointers towards melancholic depression

• Significant psychomotor change
• Sudden onset
• Reduction in oral intake of food and drink
• ‘Ideas of catastrophe’ (Ruminations / overvalued ideation/ delusions?)

Note: This presentation has features of catatonia (catatonic depression); hence, a thorough evaluation of organic causes should be considered. Read more about catatonia.

Case 2:

Learning points:  Pointers towards melancholic depression

• Ruminations
• Lack of motivation
• Early morning awakening
• Anhedonia and Guilt
• ‘Impostor syndrome’ (Ruminations of worthlessness / Self-doubt?)
• ADs resulting in poor response and increasing agitation (mixed features)

PSYCHOTIC DEPRESSION - CLINCIAL FEATURES

Psychotic major depression (PMD) is a severe form of depression with significant morbidity and mortality.

Patients with psychotic depression have double the risk of dying than non-psychotic depression and higher odds of completed suicide. [Vythilingam M et al., 2003]., [Gournellis R et al., 2018]

Psychotic depression is a specifier of MDD in DSM-5.

Psychotic depression is best conceptualised as melancholic depression with psychotic features (e.g. delusions, hallucinations, guilty ruminations).

In the DSM-5, it is divided into MDD with mood-congruent or mood incongruent psychotic features.

Patients with Psychotic depression often have a longer duration of episodes and a higher likelihood of recurrence of depression. [Keller J et al., 2007]

Data from the National Institute of Mental Health (NIMH) Study of the Pharmacotherapy of Psychotic Depression (STOP-PD) indicates that clinicians frequently miss the diagnosis of psychotic depression, in large part, due to a lack of recognition of the psychotic features.

In the STOP-PD Study, 27% of 130 diagnoses among a well-characterized sample of patients with a research diagnosis of psychotic depression were initially incorrectly diagnosed.

It is likely that the missed diagnosis rate observed in this study was a conservative estimate of the rate in the general clinical population because patients with comorbid conditions such as a history of substance abuse in the past 3 months or unstable medical conditions were excluded.

Psychotic depression was most commonly misdiagnosed as major depressive disorder without psychotic features, depression not otherwise specified (NOS), or mood disorder NOS. It was quite striking that none of the patients with missed diagnoses were considered to have a psychotic disorder. This finding suggests that the clinicians were missing the psychosis rather than the mood disorder. [Rothschild A., 2013]

Psychotic depression is associated with lower amygdala and subcallosal region of the anterior cingulate cortex (scACC) volumes and may be a marker of future risk of psychotic depression. [Keller J et al., 2008], [Bijanki K et al., 2014]

Patients with psychotic depression also show a significant reduction in hippocampal volume bilaterally, perhaps due to high cortisol states associated with psychotic depression. [Bijanki K et al., 2014]

Clinical Clues to psychosis in depressed patients [Dubovsky et al, 2021]

Symptoms: 

• Severe early morning awakening
• Extreme agitation or retardation
• Overvalued self reproach, guilt and somatic preoccupation
• Marked perplexity and cognitive dysfunction
• Significant dissociation
• Family history of psychosis
• Previous episodes of psychotic depression
• Sleep onset REM / Hypnagogic hallucinations

Key features:

Delusions in psychotic depression:

• Delusions of poverty
• Nihilistic delusions (e.g. Cotard syndrome)
• Delusions of guilt and unworthiness
• Hypochondriacal delusions

Case 1: Below is the information was obtained from the family

Case 2:

Note that the letter mentions impostor syndrome – on evaluation, the patient believed that they were not performing well at work and were going to be sacked (despite being at the place of work for 20 years).

It is important to recognise that in some cases, the delusions or ruminations may be less bizarre and may seem appropriate as exaggerations of some current situation. (as in case 2).

However, the patients continue to be in distress despite frequent reassurance and evidence to the contrary.

MELANCHOLIC DEPRESSION MANAGEMENT

Within the frontal-subcortical circuits (FSC), Dopamine (DA) is the principal neurotransmitter. As the neurobiology of melancholic depression involves the FSC with dopamine being the predominant neurotransmitter, narrow acting ADs like SSRIs may not be sufficient for an adequate response other than in cases at the milder end of the spectrum.

Thus, broad-spectrum antidepressants or dual-acting antidepressants are required that increase 5-HT, DA, NA for optimal effect.

Deficits in interest, motivation and hedonic capacity are linked to melancholic depression.

These symptoms are often associated with poor outcomes with antidepressants that selectively target the norepinephrine and serotonin systems. This same symptom constellation is thought to be most highly dependent on an intact dopamine system. [Felger J and Miller A, 2002]

The Prefrontal cortex (PFC) is a main cortical target of both NA and DA innervations, with both neuronal systems modulating PFC activity in addition to memory and attentional performance. [Xing B et al., 2016]

From a functional perspective, two functional connections stand out in their contribution to melancholic depression [Ichikawa N et al., 2020]

1. ECN-SN: Functional connections with left inferior frontal gyrus in the executive control network (ECN) and right Dorsal medial prefrontal cortex DMPFC/Frontal eye fields FEF/Supplementary motor area SMA in Salience network (SN)

1. DMN- ECN: Connections in Left DLPFC-IFG in ECN and Posterior cingulate cortex PCC/Precuneus in default mode network (DMN)

Interestingly, the functional connection (DMN-ECN) did not improve right after the antidepressant treatments, while the other functional connection (ECN-SN) was normalised. The antidepressants studied were SSRIs.

SSRIs do not act on the DMN-ECN, and evidence suggests that the mechanism of SSRIs maybe not due to the pharmacological properties of SSRIs in increasing synaptic serotonin but by the brain’s compensatory mechanisms in restoring energy homeostasis (explaining the lag effect of SSRIs). [Andrews P et al., 2015]

This suggests the need for combined treatment in melancholic depression for a broad spectrum effect. e.g. Combination antidepressants that target DLPFC (ECN) and /or neurostimulation and neurofeedback.

Note: Both cases above had trials on SSRIs without success.

Interestingly, there is a differential response to TCAs and SSRIs when age is taken into account. [Parker G., 2002]

• In individuals below the age of 46, there was no significant difference in response.
• In individuals over 46, TCA was twice as effective in those aged 46–60 years and four times more effective in those older than 60 years.

Such a phenomenon may explain why many patients with melancholia will report benefit from an SSRI for years or decades and then experience a progressive ‘poop out’ (i.e. loss of efficacy over an extended period, as opposed to ‘tolerance’ which is a more rapid phenomenon in that it occurs over days or weeks). [Parker G., 2002]

Below is a summary of management strategies in melancholic depression compiled from articles by [Wilhelm K., 2009], [Parker G., 2017], [RANZCP Guidelines] , [Giakoumatos & Osser, 2019] and personal experience.

Clinical pearls:

1. SSRIs are narrow acting antidepressants with main effects on serotonin reuptake. At higher doses, some SSRIs can have effects on NA and DA. Read more on mechanisms here.
2. SNRIs are dual-acting antidepressants with both serotonergic and noradrenergic effects. The Noradrenergic transporter (NAT) blocks dopamine reuptake in the PFC and can increase PFC dopamine (PFC has minimal Dopamine transporters (DATs)). [Xing B et al., 2016]
3. Tricyclic Antidepressants (TCAs) are broad-spectrum antidepressants increasing serotonergic, noradrenergic and dopaminergic activity. Their use is limited by their side effect profile which includes anticholinergic side effects and cardiac effects. Imipramine and nortriptyline are less sedating, while amitriptyline, doxepin, dothiepin are sedating.
4. Noradrenergic and serotonin specific antagonists (NASSAs): Mirtazapine and Mianserin. Mirtazapine predominantly acts as a serotonin antagonist (5-HT2 A and C) at 15-30 mg doses. However, the noradrenergic and dopaminergic activity requires higher doses of 45-60 mg due to presynaptic α₂-antagonism. (adrenoreceptors play a role in dopamine transmission). [Hara M et al., 2010]
5. Noradrenaline reuptake inhibitors (NARIs): Reboxetine can be used for a stimulating effect
6. Noradrenaline Dopamine Reuptake inhibitors (NDRIs): They enhance the noradrenergic and dopaminergic activity and can be particularly useful when significant fatigue and lethargy are present. e.g. Bupropion
7. Monoamine oxidase inhibitors (MAOIs) are broad-spectrum antidepressants, and dietary adjustments are required with the irreversible MAOIs.
8. Vortioxetine and agomelatine are newer antidepressants. Vortioxetine is indicated in melancholic depression as it has a broad spectrum effect. Vortioxetine has additional benefits for MDD with somatic symptoms and analgesic effects. Agomelatine can be combined with SSRIs/SNRIs/ NASSAs/ and is commonly used as an augmentation strategy in melancholic depression. Agomelatine can be safely added to other antidepressants. Fluvoxamine is the only SSRI that is contraindicated with agomelatine as it can increase levels of agomelatine (CYP1A2 inhibition).
9. A recent systematic review and meta-analysis concluded that combination treatment as a general principle seems to be more effective than monotherapy without being associated with higher numbers of patients dropping out. The combination of monoamine reuptake inhibitors (selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or tricyclic antidepressant) and α2-adrenergic receptor antagonists (mirtazapine, mianserin, trazodone) seemed to be the most effective and preferable antidepressant combination. [Henssler et al, 2022]
10. Augmentation with pramipexole at higher doses (1.0-5.0 mg/day) is evidence-based. Severe anhedonia, lack of motivation, inability to initiate behaviours and unreactive mood are predictors of response.
11. If agitation is present, APs or short term BZD may be required. If psychotic symptoms are present, AP augmentation is needed for a response (see below in psychotic depression). In such cases, ADs alone can significantly worsen agitation. (See Case 2 letter)
12. Worsening of agitation/akathisia / ‘feeling wired’ with ADs may indicate a mixed state and may require combination treatment with mood stabilisers or APs. (Read more on depressive mixed states)
13. Lithium is also an effective augmentation strategy, and lower levels are needed to treat bipolar disorder. In my clinical experience, lithium can be used to target suicidality, ruminations, residual agitation not responding to APs and mixed states.
14. Treat subclinical hypothyroidism if present. T3 and Thyroxine augmentation are effective evidence-based strategies.
15. ECT is evidence-based in severe melancholic depression
16. Ketamine has been included in the The Psychopharmacology Algorithm Project at the Harvard South Shore Program as an option if ECT is ineffective or is refused. [Giakoumatos & Osser, 2019]
17. Intranasal Esketamine is now FDA and TGA approved for treatment resistant depression. It may be an option in severe cases due to its rapid speed of onset and evidence of suicidal ideation reduction.
18. Repetitive transcranial magnetic stimulation (rTMS) is a recommended treatment in treatment-refractory depression (TRD). However, predictors of response may be linked to illness characteristics, nature of depression and severity, which is relevant to the use of rTMS in melancholic depression. [Trevizol A et al., 2020], [Kar S., 2019]

Positive predictors of response to rTMS:

• Psychomotor retardation
• Younger patients with cognitive and affective symptoms (< 45 years)
• A low score of treatment resistance
• High levels of sleep disturbance
• Short duration of episode (<4 years)
• Employment
• Higher levels of extraversion

Negative predictors of response to rTMS:

• Higher baseline severity of both depressive and anxiety symptoms was associated with a lower chance of achieving remission.
• Feelings of guilt
• Depressed mood
• Somatic symptoms
• Greater number of treatment failures
• Non-response to ECT
• Psychotic depression

16. Psychostimulants are effective augmentation agents in melancholic depression. Armodafinil can be particularly useful in co-morbid obstructive sleep apnoea (OSA) or with significant daytime fatigue. Methylphenidate and dexamphetamine can be used if armodafinil or modafinil fails or is intolerable. However, according to the RANZCP guidelines:

There is insufficient evidence to recommend the routine use of psychostimulants as an augmentation strategy.

According to Prof Gordon Parker (Black Dog Institute)  :

My fourth augmenting strategy is the use of a psychostimulant (which can be added to virtually all antidepressants – with the monoamine oxidase inhibitors or MAOIs being a clear exception).

I emphasise that I view such psychostimulants as potentially salient for only those depressed patients with melancholia – generally being ineffective and associated with dependency and tolerance in those with non-melancholic depressive conditions.

I favour methylphenidate over dexamphetamine and short-acting methylphenidate (which has a more pulsatile action) over extended-release methylphenidate.

I commence at 10 mg and generally do not need to proceed beyond 30 mg/day. In my clinical experience, it is successful as an augmentor in some 40% of melancholic patients, and tends to act like an MAOI but does not require the MAOI dietary restrictions. [Parker G, 2017]

A study evaluating psychostimulants for those with treatment-resistant unipolar or bipolar melancholic depression (and with the 61 unipolar patients having been resistant to a mean of 6.8 psychotropic drugs and a mean of 5.1 antidepressants): [Parker G et al., 2013]

The psychostimulant was judged by those with unipolar melancholia as very effective (21%) or somewhat effective (49%).

It was judged as the best antidepressant or equivalent to the previous best antidepressant by 47%; while 47% reported a sustained response.

Nevertheless, one-third of the sample experienced significant side-effects, tolerance developed in 7%, and the psychostimulant was ceased in 49% either because of side-effects or ineffectiveness.

A recent review noted: [Pary R et al., 2015]

For patients with depression who have not responded to other augmentation strategies, psychostimulants may be offered to improve mood, energy, and concentration.

For clinicians considering stimulant augmentation, modafinil and armodafinil are reasonable choices given their efficacy in double-blind, placebo-controlled trials and lower risk of misuse.

Dextroamphetamine (particularly lisdexamphetamine) and methylphenidate may be appropriate for patients who have not benefited from or tolerated modafinil or armodafinil, provided these patients do not have a medical history of cardiac disease or current substance use.

Another systematic review and meta-analysis noted :

Psychostimulants were associated with statistically significant improvement in depressive symptoms in major depressive disorder and bipolar disorder. Efficacy outcomes differed across the psychostimulants evaluated as a function of response rates. Efficacy outcomes also differed between agents used as adjunctive therapy or monotherapy. [McIntyre et al, 2017]

Read more about the mechanisms of action of methylphenidate and dexamphetamine.

Read more about the mechanisms of action of modafinil and armodafinil. 

Important: 

Switching antidepressants and/or combining antidepressants requires caution.

When switching antidepressants clinicians have to carefully balance minimising withdrawal symptoms and preventing serotonergic syndrome. This requires an understanding of half lives of antidepressants (half lives multiplied by 5 is washout period).

Diagnosis and Management of Antidepressant Withdrawal – Understanding the Hyperbolic Curve and SSRI withdrawal

Serotonergic syndrome can occur because two antidepressants with serotonergic activity are combined OR during the switch there is an overlap of two antidepressants because the half life of the initial antidepressant is long. e.g when tapering from fluoxetine to SNRI; it is important to recognise that the half life of fluoxetine metabolite is 5-7 days, thus the wash out period is approx 35 days. If an SNRI is started and the dose increased rapidly during cross tapering, there may be a period of overlap where serotonergic activity is significant.

Please refer to Switching or Augmentation Strategies in the Treatment of Major Depressive Disorder – What Does the Evidence Tell Us? for guidance.

PSYCHOTIC DEPRESSION - MANAGEMENT

The treatment of psychotic depression has not been studied to the same extent as other psychiatric disorders, and it remains an underdiagnosed and undertreated psychiatric disorder.

A systematic review and meta-analysis showed that an antidepressant and antipsychotic combination is significantly more effective than either antidepressant monotherapy or antipsychotic monotherapy for the acute treatment of psychotic depression. [Farhani A & Correll C, 2012].

This evidence is incorporated within the CANMAT, RANZCP and APA guidelines on psychotic depression treatment.

Despite the recommendations of combination AD and AP treatment in psychotic depression, the STOP-PD study (2007) showed that only 5% of patients with psychotic depression receive an adequate combination of an antidepressant and an antipsychotic.[Andreescu C, et al., 2007]

This is similar to a decade earlier which also showed low use of APs but also inadequate dose and duration of medication treatment. The most likely reason is a missed diagnosis. [Rothschild A., 2013]

According to Wijkstra J et al., 2006:

Antidepressant monotherapy and adding an antipsychotic if the patient does not respond, or starting with the combination of an antidepressant and an antipsychotic, both appear to be appropriate options for patients with unipolar psychotic depression. Antipsychotic treatment on its own appears to be ineffective.

Clinical pearls:

• Initial combinations may include SSRIs or SNRIs plus AP.
• Olanzapine is commonly used and has been studied in combination with both SNRIs and SSRIs. It has an additional sedating effect which can be useful in severely agitated patients. However, long term use can lead to weight gain and metabolic dysfunction. Quetiapine is an alternative that has also been used, but higher doses are required for an antipsychotic effect. It similarly has metabolic dysfunction as a side effect.
• APs such as Lurasidone, Brexpiprazole and Aripiprazole are metabolically friendly augmenting agents and are effective in psychotic depression. (Simplified guide to oral antipsychotics)
• Lithium is recommended as an augmentation agent if the combination of AD and AP fails. [Dubovsky et al, 2021]
• ECT has a high response rate in psychotic depression and should be considered in urgent cases or if medication trials fail. However, there can be a rapid relapse of depressive symptoms post ECT (50% relapse in 6 months in patients randomised to nortriptyline monotherapy, nortriptyline plus lithium, or placebo), and this may indicate the need for ongoing AD and antipsychotic treatment for longer periods after the acute depressive episode has been treated with ECT. [ECT RANZCP Guidelines summary]
• ECT is superior to rTMS in psychotic depression, and there is insufficient evidence to recommend rTMS in psychotic depression. [Ren J et al., 2014]

How long should the medication be continued?

The optimal maintenance period is currently not known. The STOP-PD II aimed to address this issue. [Flint A., 2019]

The study was a randomised clinical trial of 126 adults with psychotic depression in remission (≥18 years old) (treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial.)

Only 20.3% of trial participants randomized to sertraline plus olanzapine experienced a relapse after 36 weeks versus 54.8% randomized to sertraline plus placebo, which was a statistically significant difference.

These results suggest that risk for relapse is much greater if the antipsychotic is discontinued after about 20 weeks of combined treatment (even though one in five patients relapsed with ongoing antipsychotic treatment). Although most relapses occurred within the first 2 months, it’s unknown how much longer than an additional 2 months the antipsychotic must be continued to attenuate this risk. The benefits of continuation must be balanced against risks for weight gain and metabolic syndrome.

An editorialist suggests that, in the absence of more definitive data, clinicians should continue the antipsychotic for at least 4 months after response, then gradually taper it while observing for signs of relapse — and reinstituting the last effective dose if these signs occur. [Roy-Byrne P, 2019]

In my clinical experience, the antipsychotic needs to be continued for at least 6 months before any attempts at a reduction is considered. The AD should be continued for at least 12 months. Many patients may need long term AD and AP treatment. Premature discontinuation poses a significant risk of relapse.

CASE STUDIES

Case 1:

• The patient was on Citalopram 20 mg OD (SSRI). He had previously had two episodes 23 and 16 years ago treated with Sertraline and Citalopram.
• The patient responded to a combination of SNRI + Mirtazapine (60 mg nocte) + Low dose antipsychotic – Response in 4 -6 weeks.
• The patient is in complete remission after a mild hypomanic episode at 6 months, responding to dose reduction and optimisation.
• The patient is stable on low dose SNRI + Mirtazapine 30 mg nocte + Low dose antipsychotic.
• It is important to note that psychotic depression is a correlate of bipolar depression. (Read more about bipolar depression and depressive mixed features)
• The patient is in remission for >2 years
• MRI: Vascular features
  

Patchy confluent FLAIR hyperdensities in the periventricular white matter and small patchy and small rounded FLAIR hyperdensities in the subcortical and deep white matter is consistent with mild chronic small vessel white matter ischaemia.

Case 2:

The patient responded to SNRI + Armodafinil +  low dose antipsychotic. As a result, the patient is back to full-time work and is in remission for > 2 years.

Clinical pearls:

• In my personal experience, the combination of an SNRI with another dopaminergic agent can be successful.

Essentially you create your own TCA by this combination; a broad spectrum antidepressant.

I call the above Triple Therapy and have found it a beneficial treatment in many cases of melancholic depression with agitation/psychosis.

• If mixed features/agitation/ruminations/ overvalued ideation / psychotic features are present, I consider an antipsychotic from the start. Clonazepam 0.5 mg short term can provide additional anti-agitative properties if a non-sedating AP is used.
• The second antidepressant is introduced only if the initial combination of AD and AP has not worked. In many cases, a single antidepressant with antipsychotic suffices.
• Triple therapy may be reserved for severe cases that have not responded to other treatments.
• White matter hyperintensities are associated with vascular deficits. Vascular depression tends to be more severe, often requires broad-spectrum ADs, is associated with cognitive deficits, and can be associated with other vascular factors that should be proactively managed. (e.g. HT, diabetes, alcohol, smoking etc.)
• A case series of triple antidepressant combinations (ADs not at maximal doses) showed a benefit for treatment-resistant patients. The author proposed exploiting the synergism between various ADs for maximal benefit. [Restifo S et al., 2012]

The term ‘polypharmacy’ generally carries a negative connotation which is actually more correctly related to the notion of irrational polypharmacy. Less mention is usually made, however, of rational polypharmacy which involves pharmacodynamic synergism and has long been established as good practice in various clinical fields such as oncology, anaesthesia, hypertension, pain management and so on. [Restifo S et al., 2012]

SUMMARY

Melancholia has been described since Hippocratic times and was considered part of the manic depressive spectrum of mental illness.

Melancholic and psychotic depressions are presentations of depression with a unique set of clinical features.

Traditional DSM -5 criteria do not include changes in volition, slowing of speech, or physical symptoms such as constipation, which may contribute to underdiagnosis. [Kendler K, 2016]

Genetic and biological factors are often present. Both melancholic and psychotic depression is associated with significant morbidity and mortality.

Studies show that these types of depressions, particularly psychotic depression, may be under-recognised and undertreated.

Clinicians should familiarise themselves with the core clinical features for each.

Treatment requires broad-spectrum antidepressants in melancholic depression and augmentation strategies as second and third-line treatments.

Psychotic depression requires antidepressants and antipsychotics as initiating treatments.

QUIZ