Mood disorders: Clinical practice

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Mood disorders: Clinical practice

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A 17-year-old girl is brought to the emergency room by her parents after she was found trying to ingest bleach. She appears restless and agitated, and says that she is a terrible person who does not deserve to be alive. Her parents report that she had been more talkative and irritable than usual. However, since yesterday, she has been confused and withdrawn. She had not slept more than four hours a night for the last two weeks, and she was fired from her summer job due to making inappropriate sexual innuendos. She tells you that her bad behaviors have been broadcasted on the national news, and that the police are looking for her, however, neither of these things have happened. Which of the following is the most appropriate medication to be administered as a first-line therapy for her condition?

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Content Reviewers:

Rishi Desai, MD, MPH

Mood disorders are a group of illnesses that describe serious changes in the emotional status that can interfere with day-to- day activities like working, studying, eating, and sleeping. Mood disorders can precipitate a substance addiction, and in some cases can lead to suicide.

Risk factors for mood disorders include a family history and personal trauma. However, the underlying cause is poorly understood. There’s usually an imbalance of serotonin, norepinephrine, and dopamine, which are neurotransmitters that help regulate mood, reward-motivated behavior, appetite, and sleep

Each of these neurotransmitters is thought to have an impact on specific symptoms, like norepinephrine on anxiety or attention, serotonin on obsessions and compulsions, and dopamine on attention, motivation, and pleasure.

Now, depression has also been associated with hyperactivity of the hypothalamic–pituitary–adrenal or HPA axis, leading to increased cortisol levels, as well as decreased hippocampal and frontal lobe volumes, decreased sleep latency and slow-wave sleep.

Mood disorders can be seen as a spectrum. At one end of the spectrum we have depressive disorders which include major depressive disorder; substance or medication-induced depressive disorder, depressive disorder due to another medical condition, adjustment disorder with depressed mood, premenstrual dysphoric disorder and persistent depressive disorder (previously known as dysthymia).

All of these are characterized by depressive episodes, which consist of nine major symptoms - the exception being persistent depressive disorder which accounts for only six of the milder symptoms.

First, a person feels depressed, hopeless, or lacks a sense of purpose most of the day, every day. Second, there’s anhedonia - which means a diminished interest in an activity that used to be really pleasurable - like no longer enjoying cooking or gardening, if that was once a hobby. Third, either weight gain or weight loss, because of an increase or decrease in appetite. Fourth, is sleeping too much or too little from what used to feel normal. Fifth, there may be too much energy - a person might start pacing around, or too little energy - a person might feel chronically fatigued. Sixth, a person might have persistent feelings of worthlessness. Seventh, a person might feel excessive guilt. Eighth, a person may have difficulty concentrating. And finally, ninth, a person might have recurrent thoughts of death or suicidal ideation with or without a specific plan.

The symptoms, regardless of the episode’s nature or disorder type, must be present for the entire duration of the episode and must affect most of the day, while also negatively impacting a person’s life.

The archetype of the depressive disorders is major depressive disorder. According to DSM-5, the disorder is characterized by episodes that last for at least two weeks and which involve changes in affect, cognition, and neurovegetative functions such as decreased ability to concentrate and fatigue.

The episodes must include five of the key symptoms that describe depressive episodes, and two of them should be the persistence of depressive mood and anhedonia, while the rest can be either of the remaining seven.

Family and friends may also be helpful by reporting symptoms that may otherwise be ignored or unobserved by the individual, especially when it comes to weight changes and loss of interest in pleasurable activities that the individual once enjoyed which are easier for an outsider to notice.

Other tools include self-rating symptom scales like the PHQ Depression Scale or the Hamilton Rating Scales, which an individual can use to rate how they feel.

Also, it is important to understand that periods of sadness and grief are normal aspects of every individual's life. They should not be diagnosed as a major depressive episode unless criteria are met for severity, five out of nine symptoms; duration, symptoms present most of the day for nearly every day over at least 2 weeks; and impairment,

Now, there are also subtypes of major depressive disorder- like depression with atypical features, postpartum depression, major depressive disorder with seasonal pattern-- previously known as seasonal affective disorder and major depressive disorder with psychotic features.

They all share the same symptoms as major depressive disorder but are distinguished by having a specific trigger, or in the case of atypical depression, unique features.

Depression with atypical features is the most common subtype and has two unique features. One is mood reactivity, and it’s when patients have an improved mood when exposed to pleasurable or positive events.

Another is rejection sensitivity and it’s when patients feel anxious and overreact at the slightest evidence of rejection. Other key features include hyperphagia, hypersomnia and leaden paralysis, which is an unusually heavy feeling in the arms and legs.

Postpartum depression, which has an incidence rate of 10-15%, is thought to start after childbirth and have symptoms that last at least two weeks.

In many cases, however, the onset of depression occurs before childbirth, so a more accurate term is depressive disorder with peripartum onset. In other words, the onset happens during pregnancy or four to six weeks following delivery, but can appear up to one year later.

The exact cause isn’t understood, but it’s likely related to changes in estrogen and progesterone levels, along with the emotional and physical stress that can accompany the birth of a child.

Postpartum depression has to be differentiated from postpartum blues, where the incidence rate is 50-85%! This starts 2-3 days after delivery and typically resolves within 10 days.

Next up is major depressive disorder with seasonal pattern, where, symptoms appear during cold seasons due to a decreased exposure to sunlight, which also seems to improve them.

Diagnosis requires at least two depressive episodes to have occurred during cold months for the past two years, with no history of depressive episodes appearing in a non seasonal pattern.

There’s also major depressive disorder with psychotic features, previously known as psychotic depression, which is when depression is accompanied by psychotic features, including hallucinations or delusions.

These features are usually in alignment with the person’s low mood, and may center around guilt, punishment, inadequacy, disease or death. The key here is that the psychotic features occur only during episodes of major depression.

This comes in contrast with schizoaffective disorder, which requires the presence of psychotic symptoms for at least two weeks without any mood symptoms present.

Now, it’s important to differentiate major depressive disorder from substance or medication-induced depressive disorder, depressive disorder due to another medical condition, adjustment disorder with depressed mood and premenstrual dysphoric disorder.

First, substance or medication-induced depressive disorder is when abuse or withdrawal from a substance like alcohol, opioids, cocaine or amphetamines causes the depressive episode.

For example, a depressed mood that occurs only in the context of withdrawal from cocaine would be diagnosed as cocaine-induced depressive disorder.

Depressive disorder due to another medical condition can be distinguished from major depression based on three particularities: first, the absence of depressive episodes prior to the onset of the medical condition. Second, the condition has the potential to cause depressive disorder, especially if it causes severe pain and physical disabilities, and third, symptoms resolve once the illness has been treated, or worsen as the condition gets worse too.

Next, in adjustment disorder with depressed mood, symptoms appear within 3 months of an identifiable stressor, such as changing schools or jobs, marriage, the loss of a relationship, or a severe illness, and rarely last more than 6 months after the stressor ends.

These symptoms lead to marked distress and/or functional impairment, but do not meet criteria for major depressive disorder.

Then, there’s premenstrual dysphoric disorder, which is when depressive symptoms occur during the luteal phase of the menstrual cycle - that is, 2 weeks before menstrual bleeding, and then the symptoms usually remit a few days after the onset of menses.

Another mental health condition that can have depressive symptoms is persistent depressive disorder, a condition that as mentioned earlier was previously called dysthymia.

Here the symptoms of depression are more mild, meaning two or more of the following: a change in appetite, a change in sleep, fatigue or low energy, reduced self-esteem, decreased concentration or difficulty making decisions, and feelings of hopelessness or pessimism.

And these symptoms persist over longer periods of time, specifically two or more years in adults and one or more years in children or adolescents, with no symptom free period for >2 months. In contrast, the episodes in major depressive disorder last a medium of four weeks.

If, however, individuals present depressive symptoms that don’t meet the full criteria for any of the disorders above, clinicians can group them in two new disorders.

The first one is other specified depressive disorder, where the clinician knows and chooses to specify the triggering factor, and the second one is unspecified depressive disorder, where the partial symptoms are not attributable to any specific factor.

Now let’s switch gears and look at the other end of the spectrum, which includes conditions characterized by manic or hypomanic episodes, like bipolar I, II and cyclothymia.

A manic episode lasts for at least a week and is a state where at least three of the following seven symptoms should be present. First, individuals might feel an inflated self-esteem or grandiosity. Second, they might be more talkative than usual. Third, they might feel an urgency to keep talking. Fourth, they might have racing thoughts. Fifth, they might feel easily distracted or might pay excessive attention to irrelevant things, which might make a person move from one task to another without finishing any of them. Sixth, they might feel the need to achieve certain things, for example, an individual might spend more than twenty hours a day on social media just to reach a certain number of followers. Seventh, individuals might get involved in reckless things like sexual indiscretions or bad financial investments.

A hypomanic episode, on the other hand, includes a milder version of at least three of the same symptoms, and it lasts at least four days.

It’s important to distinguish between bipolar I, bipolar II, and cyclothymia. Bipolar I disorder has at least one manic episode that’s preceded or followed by a hypomanic or major depressive episodes.

Now sometimes, major depressive disorder can also be accompanied by hypomania or mania symptoms, and that’s called depressive disorder with mixed features.

The difference is that in a depressive episode with mixed features, the full criteria are met for a major depressive episode, but not for a manic or hypomanic one.