Learn — Mood disorders & suicide

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Tricyclic antidepressants — side effects

Tricyclic antidepressants block the reuptake of serotonin and noradrenaline at the synapse, which is how they treat depression, but they also block muscarinic, histamine H1 and alpha-1 adrenergic receptors and fast sodium channels in the heart, which is where almost all their adverse effects come from. They are as effective as newer antidepressants but are no longer first line because they are poorly tolerated and dangerous in overdose, a serious matter in depression, where the person may take the whole supply at once.

The drugs and their usual adult ranges: amitriptyline and imipramine about 75 to 150 mg a day (up to 300 mg in resistant illness), nortriptyline about 75 to 150 mg a day and better tolerated in older people, and clomipramine, the most serotonergic, up to about 250 mg a day and the tricyclic used for obsessive-compulsive disorder.
Anticholinergic effects are the commonest reason for stopping: dry mouth, blurred vision, constipation, urinary retention, tachycardia, and confusion or delirium in older people; they are also why the drugs are avoided in narrow-angle glaucoma and in prostatic enlargement.
Cardiovascular effects are the dangerous ones: postural hypotension from alpha-1 blockade with falls in older patients, sinus tachycardia, and quinidine-like slowing of cardiac conduction that widens the QRS complex and prolongs the QT interval.
Other effects are sedation and weight gain from histamine blockade, lowering of the seizure threshold, sexual dysfunction, and a switch into mania in a person with bipolar disorder if the drug is given without a mood stabiliser.
Response takes time: sleep and appetite improve in the first one to two weeks, but the mood lifts only after about two to four weeks, and the drug is continued for at least six months after remission of a first episode; abrupt stopping causes a discontinuation syndrome with flu-like symptoms, nausea and vivid dreams, so it is tapered.
Overdose is a medical emergency and the leading cause of death from these drugs: anticholinergic delirium, seizures, hypotension, coma and cardiac arrhythmia, with a QRS duration over 100 milliseconds predicting seizures and over 160 milliseconds predicting ventricular arrhythmia; treatment is intravenous sodium bicarbonate, airway support, benzodiazepines for seizures and cardiac monitoring, and class I antiarrhythmics such as procainamide are contraindicated.
Other named uses in the examination: amitriptyline for neuropathic pain and migraine prophylaxis, imipramine for nocturnal enuresis in children, and clomipramine for obsessive-compulsive disorder.
Combining a tricyclic with a monoamine oxidase inhibitor risks serotonin syndrome and hypertensive crisis, so a washout of about two weeks is observed between them.

Depression — neurotransmitter deficits

The monoamine hypothesis holds that depression is associated with reduced availability of the monoamine neurotransmitters serotonin, noradrenaline and dopamine at the synapse, which is why every established antidepressant raises one or more of them. The hypothesis is incomplete rather than wrong: the drugs raise monoamine levels within hours but the mood lifts only after two to four weeks, so current models add downstream receptor changes, reduced brain-derived neurotrophic factor, hyperactivity of the hypothalamic-pituitary-adrenal axis with raised cortisol, and glutamate and GABA abnormalities.

Serotonin deficiency is linked to low mood, anxiety, irritability, disturbed sleep and appetite, obsessive symptoms and impulsive suicidal behaviour; low cerebrospinal fluid 5-hydroxyindoleacetic acid, the main serotonin metabolite, has been associated with violent suicide attempts.
Noradrenaline deficiency is linked to loss of energy, poor concentration and reduced alertness; dopamine deficiency in the mesolimbic reward pathway is linked to anhedonia, apathy and loss of motivation, which is why bupropion, which acts on dopamine and noradrenaline, is used when anhedonia dominates.
The drug classes map onto the transmitters: selective serotonin reuptake inhibitors (fluoxetine, sertraline, escitalopram) act on serotonin alone and are first line; serotonin-noradrenaline reuptake inhibitors (venlafaxine, duloxetine) act on both; tricyclics act on both plus several unwanted receptors; monoamine oxidase inhibitors block the enzyme that degrades all three.
Atypical agents fill in the picture: mirtazapine blocks presynaptic alpha-2 receptors and so increases noradrenaline and serotonin release while sedating and stimulating appetite through H1 blockade, and bupropion inhibits noradrenaline and dopamine reuptake and is contraindicated where the seizure threshold is already low, including in eating disorders.
The delay in response is the clinically important fact: sleep and appetite often improve within one to two weeks, but the mood usually lifts only after two to four weeks and a full trial is six to eight weeks at an adequate dose before the drug is judged to have failed.
Beyond monoamines, the accepted contributors are a raised cortisol with a blunted dexamethasone suppression response, reduced brain-derived neurotrophic factor and hippocampal volume loss, disturbed circadian rhythm with early-morning waking and diurnal variation, and thyroid dysfunction, which is why thyroid function is checked before a depression is called treatment-resistant.
The glutamate system explains the newest treatments: ketamine and esketamine act on NMDA receptors and can lift severe depression and suicidal ideation within hours rather than weeks, which is itself evidence that the monoamine account is not the whole story.
Serotonin excess is as important to recognise as deficiency: combining serotonergic drugs, or adding tramadol, pethidine, linezolid, triptans or St John's wort, can cause serotonin syndrome with altered mental state, autonomic instability and neuromuscular excitation.

Depression vs normal grief

Grief, or uncomplicated bereavement, is the normal and self-limiting response to a loss, in which sadness comes in waves triggered by reminders of the person who died, self-worth stays intact and function gradually returns. A major depressive episode differs in being pervasive rather than wave-like, in attacking the person's own worth, in impairing function for at least two weeks, and in producing suicidal thoughts about ending one's own life rather than a wish to join the deceased.

Mood pattern: in grief the dysphoria comes in waves or pangs, eases in company and with distraction, and lightens over weeks, whereas in depression the low mood and inability to feel pleasure are constant, present most of the day nearly every day, and are not relieved by company.
Self-esteem: grief preserves self-worth, and any guilt is specific and concerns the death itself, such as not having called the doctor sooner; depression brings global worthlessness and pervasive self-blame that go far beyond the loss.
Thoughts of death: the bereaved person may wish to be with the person who died or feel life is empty, while the depressed person feels they deserve to die, that others would be better off, or plans an act of self-harm.
Course and function: grief improves progressively, and the person returns to work and to caring for others within weeks to a few months, while depression persists or worsens, with marked psychomotor retardation, prolonged functional impairment and, in severe cases, mood-congruent delusions and hallucinations.
Hallucinatory experiences of hearing or briefly seeing the person who died are common in normal grief and are not psychosis, provided insight is retained and the experience is limited to the deceased.
DSM-5 removed the bereavement exclusion, so a major depressive episode is diagnosed on its own criteria even within the first weeks after a death, on the reasoning that bereavement does not protect against depression and depressed bereaved people benefit from treatment.
Prolonged grief disorder is now a recognised diagnosis: DSM-5-TR requires the death to have occurred at least 12 months earlier in adults, and 6 months in children and adolescents, with persistent intense yearning or preoccupation and associated symptoms causing impairment; ICD-11 uses a threshold of persistence for at least 6 months beyond what the person's culture expects.
Management differs accordingly: normal grief needs presence, permission to talk about the person, practical support and time, not medication, while depression needs assessment of suicide risk, an antidepressant with psychotherapy, and follow-up; a hypnotic for a few nights may be reasonable, but sedating a bereaved person routinely delays the work of grieving.

Omega sign in depression

The omega sign is a vertical furrow between the eyebrows shaped like the Greek letter omega, produced by sustained contraction of the corrugator supercilii muscle in a person with severe depression. It belongs with the other observable facial signs of melancholia and is a supportive clinical observation rather than a diagnostic test, since the same furrow can be produced by pain, concentration or bright light.

The sign is produced by tonic overactivity of the corrugator supercilii, the muscle that draws the eyebrows together, and it persists rather than coming and going with the conversation.
It is usually taught alongside Veraguth's fold, the oblique upward-angled fold of the upper eyelid described in depression and sometimes seen in people who are simply preoccupied, and both belong to the older descriptive psychiatry that the examination still draws on.
The other observable features of severe depression that the nurse records are downcast eyes with reduced eye contact, a downturned mouth, reduced blinking, stooped posture, slow and quiet speech with delayed replies, and psychomotor retardation.
The sign is sensitive to nothing and specific to nothing on its own: it supports a clinical impression when it appears with the other features and disappears as the depression responds to treatment, and its reversal has been used as one crude marker of improvement.
It has no role in diagnosis, which rests on the DSM-5-TR or ICD-11 criteria and on structured tools such as the PHQ-9, the Hamilton Rating Scale for Depression and the Beck Depression Inventory.
The nursing value of the sign is that it is one of the observations that alerts the ward to a person who is not saying how bad they feel, which matters because people in Indian clinical practice frequently present depression somatically rather than as low mood.

Clinical features of depression

A major depressive episode is diagnosed when at least five of nine symptoms have been present during the same two-week period, representing a change from previous functioning, and at least one of them is depressed mood or loss of interest and pleasure. The nine are depressed mood, anhedonia, significant appetite or weight change, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, worthlessness or excessive guilt, poor concentration or indecisiveness, and recurrent thoughts of death or suicide; the symptoms must cause distress or impairment and must not be better explained by a substance or a medical condition.

The mnemonic SIG E CAPS covers the criteria other than mood: Sleep, Interest, Guilt, Energy, Concentration, Appetite, Psychomotor change and Suicide; five symptoms including mood or anhedonia, for two weeks, is the threshold.
Melancholic or somatic features carry weight in the examination and in practice: early-morning waking about two hours before the usual time, diurnal variation with the mood worst in the morning, marked psychomotor retardation, loss of appetite with weight loss, loss of libido and a complete inability to take pleasure in anything.
Severe depression may carry mood-congruent psychotic features, typically delusions of guilt, poverty, nihilism or illness and derogatory auditory hallucinations, and it may present as depressive stupor, in which the person is mute, immobile and not eating; both are indications for urgent treatment.
In India depression very often presents somatically with headache, body ache, burning feet, giddiness and fatigue rather than with a complaint of sadness, so the nurse screens the frequent attender in a general clinic rather than waiting to be told about mood.
Screening and rating tools: the PHQ-9 is the standard self-report screen with scores of 5, 10, 15 and 20 marking mild, moderate, moderately severe and severe depression, while the Hamilton Rating Scale for Depression and the Beck Depression Inventory are clinician-rated and self-rated alternatives; item 9 of the PHQ-9 asks about self-harm and must never be skipped.
Physical causes must be excluded before a diagnosis is settled: hypothyroidism, anaemia, vitamin B12 deficiency, diabetes, stroke, Parkinson's disease, malignancy, and drugs such as steroids, isotretinoin, interferon, propranolol and some hormonal contraceptives.
Treatment is a selective serotonin reuptake inhibitor with psychotherapy for moderate to severe illness, psychotherapy alone for mild illness, and electroconvulsive therapy where there is high suicide risk, psychotic depression, stupor, refusal of food or a failure of drug treatment; the antidepressant is continued for at least six months after remission of a first episode, and for years after recurrent episodes.
Recovery follows a known order: sleep and appetite improve first, energy and concentration next, and mood last, which is why the period of returning energy with persisting hopelessness is the most dangerous for suicide.
Under the Mental Healthcare Act 2017 a person who attempts suicide is presumed, unless proved otherwise, to be under severe stress and is not to be tried or punished for it, and the government is obliged to provide care, treatment and rehabilitation to reduce the risk of a repeat attempt (Section 115); the nurse therefore treats an attempt as a health emergency and never as a police matter.

Bipolar disorder

Bipolar disorder is a recurrent mood disorder in which episodes of mania or hypomania alternate with episodes of depression and with periods of normal mood. A manic episode is a distinct period of at least one week of abnormally elevated, expansive or irritable mood together with a persistent increase in goal-directed activity or energy, severe enough to impair function, to need hospital admission or to be accompanied by psychotic features; the one-week rule is waived when the person has to be admitted.

The symptoms of mania are remembered as DIG FAST: Distractibility, Indiscretion with risky sexual, financial or business behaviour, Grandiosity, Flight of ideas, increased Activity or psychomotor agitation, reduced need for Sleep with the person feeling rested after two or three hours, and Talkativeness with pressure of speech; three of these are needed with elevated mood and four when the mood is only irritable.
Hypomania lasts at least four consecutive days with the same kind of symptoms but without marked impairment of function, without psychotic features and without the need for admission, and it is observable by others as a clear change from the person's usual self.
Bipolar I disorder requires at least one manic episode, and a depressive episode is usual but not required for the diagnosis; bipolar II disorder requires at least one hypomanic and at least one major depressive episode and no full manic episode ever; cyclothymic disorder is at least two years of fluctuating hypomanic and depressive symptoms that never meet full criteria, and one year in children and adolescents.
Rapid cycling means four or more mood episodes in twelve months and is commoner in women, in bipolar II and after antidepressant exposure; a mixed presentation, in which depressive and manic features occur together, carries the highest suicide risk of all and is coded as a with-mixed-features specifier in DSM-5-TR.
Acute mania is treated with lithium, sodium valproate or carbamazepine, usually combined with an atypical antipsychotic such as olanzapine, risperidone, quetiapine or aripiprazole, with a short course of a benzodiazepine for sleep and agitation; electroconvulsive therapy is used for severe, treatment-resistant or life-threatening mania and in pregnancy.
Bipolar depression is not treated with an antidepressant alone, because that risks a switch into mania or into rapid cycling; quetiapine, lamotrigine, lithium or an olanzapine-fluoxetine combination are the options, and any antidepressant is given under the cover of a mood stabiliser.
Sodium valproate is avoided in women who can become pregnant because of neural tube defects and neurodevelopmental harm, carbamazepine induces liver enzymes and reduces the effectiveness of oral contraceptives, and lamotrigine must be titrated slowly because of the risk of Stevens-Johnson syndrome.
Nursing care in acute mania is structured around reducing stimulation and protecting the body: a quiet low-stimulus environment, short firm consistent interactions, finger foods and a high-calorie fluid intake because the patient will not sit to eat, enforced rest periods, protection of the person's money, reputation and sexual safety, and firm limits set without argument.

Manic-depressive disorder

Manic-depressive disorder, or manic-depressive illness, is the older name for what is now called bipolar disorder, and it comes from Emil Kraepelin's manic-depressive insanity, the category he set against dementia praecox at the end of the nineteenth century. The term is no longer used in the current classifications, which speak of bipolar and related disorders in DSM-5-TR and of bipolar type I and type II disorder in ICD-11, but it survives in older textbooks and in examination questions, where it means the same illness.

Kraepelin's dichotomy separated manic-depressive insanity, which ran an episodic course with recovery between episodes, from dementia praecox, which he described as progressive deterioration; that division is the origin of the modern split between mood disorders and schizophrenia.
Kraepelin grouped all recurrent mood illness together, including what would now be called recurrent depressive disorder; the separation of unipolar from bipolar illness came later, from Leonhard's work in the 1950s, and is the reason the modern name refers to two poles.
The modern equivalents are bipolar I disorder, which needs at least one manic episode of at least one week or requiring admission, and bipolar II disorder, which needs at least one hypomanic episode of at least four days with at least one major depressive episode and no history of mania.
The features, the course and the treatment are those of bipolar disorder: lithium, sodium valproate or carbamazepine with an atypical antipsychotic in acute mania, mood stabiliser cover for any depressive treatment, electroconvulsive therapy for severe or resistant episodes, and long-term prophylaxis with psychoeducation.
Terminology matters in the ward as well as the examination: the current classifications describe a person as having bipolar disorder rather than labelling the person by the illness, and using the older term with a patient can carry stigma the newer one avoids.
Two related terms often appear in the same question: cyclothymia, the chronic low-grade fluctuation of hypomanic and depressive symptoms over at least two years, and dysthymia, now called persistent depressive disorder, the chronic low mood lasting at least two years without meeting the criteria for a major depressive episode.

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