Major Depressive Disorder (MDD) Treatment: Assessment & Therapy PDF

1. MDD is also called unipolar depression, or just depression. MDD is diagnosed when a patient has at least five of the following symptoms almost every day for at least 2 weeks: a. Must have a depressed mood or anhedonia (loss of interest in pleasurable activities)....

1. MDD is also called unipolar depression, or just depression. MDD is diagnosed when a patient has at least five of the following symptoms almost every day for at least 2 weeks: a. Must have a depressed mood or anhedonia (loss of interest in pleasurable activities). b. Additional symptoms include sleep disturbances, changes in weight or appetite, decreased energy, feelings of guilt or worthlessness, psychomotor retardation or agitation, decreased concentration, and suicidal ideation. c. The symptoms must interfere with the patient’s everyday ability to function. 2. Persistent depressive disorder (dysthymia): Chronic depressed mood occurring more days than not for at least 2 years but that does not meet the criteria for MDD.  Assessment of the Patients 1. Psychiatric history 2. Clinician rating scales 3. Patients rating scales 4. Physical examinations and lab tests 5. Biologic testing 6. Medication and substances 7. Suicidal ideation  Clinician rating scales Hamilton Rating Scale for Depression (HAM-D/HDRS) Enrolment scale> 18 (moderate-severe), response=50% reduction Remission ≤ 7 Clinical Global Impression Scale (CGI) Montegomry-Asberg Depression Rating Scale (MADRS)  Patient rating scales Patient-completed a. Patient Health Questionnaire-9 (PHQ-9) is based on rating instruments. the DSM-5 diagnostic criteria for major depression. Answers to the questions are used b. Beck Depression Inventory (BDI) to identify and assess the level of depression. c. Quick Inventory of Depressive Symptoms (QIDS) d. Geriatric Depression Scale (GDS)  Physical examination and laboratory tests: Necessary to rule out physical causes (e.g., thyroid disorders, vitamin deficiencies) that may mimic symptoms of depression. Biologic testing: Depression is commonly associated with abnormalities in the dexamethasone suppression test and tests of the thyroid axis. However, these tests are not routinely used in clinical practice. Medications and substances (e.g., interferons, benzodiazepines, barbiturates, alcohol, central nervous system [CNS] depressants, withdrawal from stimulants [cocaine, amphetamines]) can have depression as an adverse effect. Pharmacists should perform a medication and substance use review to identify possible causes. All patients should be screened for suicidal ideation.  Therapeutic Options Non-pharmacologic treatment options Examples include interpersonal psychotherapy and CBT. It takes longer to achieve effective results with psychotherapy than with pharmacotherapy. Psychotherapy may have broader and longer-lasting effects than pharmacotherapy monotherapy. Psychotherapy is recommended as monotherapy for initial treatment in patients with mild to moderate MDD (CBT and interpersonal therapy have the best evidence). Psychotherapy combined with pharmacotherapy is recommended for moderate to severe depression. Combination is more effective than either intervention alone.  Electroconvulsive therapy (ECT) Option for refractory depression, depression in pregnancy, psychotic depression, and other conditions for which medications may not be optimal or effective. The usual induction cycle is two or three treatments per week for 6–12 treatments. Maintenance dosing is individualized to the patient, and frequency can vary from weekly to monthly. Temporary memory loss is common, and medications that affect seizure threshold must be tapered or held before treatment. ECT is also suggested as initial treatment if symptoms are severe or life threatening.  Pharmacotherapeutic Options Selection: All antidepressants are considered Antidepressant equally efficacious. therapy may lead to a more rapid response than psychotherapy, but First-line medications Consider possible drug- when discontinued, include selective serotonin drug and drug-disease reuptake inhibitors (SSRIs), interactions, concurrent there is a risk of serotonin-norepinephrine illnesses, prior responses, relapse and reuptake inhibitors (SNRIs), family members’ prior adverse effects. bupropion, mirtazapine, responses, patient and vortioxetine. preference, and cost.  Adequate trial: An adequate trial includes the correct drug for the patient and a therapeutic dose for an appropriate duration. A therapeutic trial lasts 4–8 weeks. Response and remission: A response is usually defined as a 50% reduction in symptoms. Remission is a return to normal mood (e.g., HAM-D of 7 or less; PHQ-9 less than 5). Remission is also defined as at least 3 weeks with no symptoms of depressed mood and anhedonia and no more than three remaining symptoms of depression. Remission is the goal of therapy. Optimizing the dose or duration is important for achieving remission.  Treatment phases a. Acute i. The goal of this phase is remission. ii. Onset of antidepressant effect: Physical symptoms (energy levels, sleep disturbances) improve before affective symptoms. For this reason, patients with suicidal ideation should be closely monitored. Early response (20%–30% reduction in symptoms) in the first 2–4 weeks is a strong predictor of remission at 12 weeks. A patient who has a partial response in the first 4 weeks should be allowed a longer trial (and at the full therapeutic dose) before moving on to other therapy. In general, it takes 4–6 weeks to see the full effect of antidepressants, given the correct drug, dose, and adherence, but it may take as long as 8 weeks to see a response. Remission may take up to 12 weeks. iii. Monitoring therapy: Patients should be monitored for response through interviews or by repeating rating scales. In addition, patients (and their support systems, if available) should be educated about therapy and closely monitored for adverse effects. Although most of the adverse effects are not life threatening, they do affect adherence. iv. Nonresponders: A nonresponder can be changed to another antidepressant within either the same class or a different class. A patient who does not respond to one SSRI may respond to another in the same class, as shown in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.  b. Maintenance i. Once a patient has achieved remission, treatment should continue for at least another 6–9 months. ii. Those with risk factors for recurrent depression should receive treatment for 2 years or longer. Risk factors include: frequent, recurrent episodes; severe episodes (including psychosis, severe impairment, or suicidality). chronic episodes. presence of comorbid psychiatric or medical conditions. presence of residual symptoms or difficult-to-treat episodes.  Efficacy of antidepressants according to rigorous clinical trials occurs in 60%–70% of patients, regardless of drug. Effectiveness, which is more reflective of clinical practice, is lower, about 50%–60%. The remission rate with one antidepressant trial is about 30%, as seen in the STAR*D trial. Drug interactions: Many antidepressants are metabolized or inhibited by CYP enzymes. All antidepressants have an FDA black box warning for an increased risk of suicidal thinking and behaviors in children, adolescents, and young adults (up to 24 years of age). Risk is highest at treatment initiation or dose adjustment. Other signs to watch for include agitation and anxiety (activation syndrome) and other symptoms that are unlike the patient’s presenting symptoms of depression.  Partial Response to Antidepressant Treatment 1. Ensure the patient is adherent and has received a therapeutic trials of medication. 2. Patients can either be changed to a new antidepressant or receive adjunctive therapy. 3. An antidepressant with a different mechanism of action can be added (e.g., bupropion or mirtazapine to an SSRI or SNRI). Data are not strong for this practice. Use caution when combining agents to avoid potential serotonin syndrome with at-risk agents. 4. SGAs may be used as adjuncts to antidepressant therapy. Almost all SGAs have been used, but only aripiprazole, brexpiprazole, and quetiapine have received FDA approval for this indication. Evidence also supports the use of risperidone. Olanzapine in combination with fluoxetine is also approved, but specifically for treatment-resistant depression. 5. Ketamine infusions are used off-label for depression and suicidality, particularly in patients who are not responsive or who are only partly responsive to antidepressants. 6. Other adjuncts include lithium, liothyronine, stimulants (including methylphenidate and modafinil), and buspirone.  Treatment-Resistant Depression 1. Has many definitions; usually defined as inadequate response to at least two antidepressants. 2. FDA-approved treatment options: a. Olanzapine plus fluoxetine: Initial dosing is 6 mg/25 mg once daily; usual dosing is 6–18 mg/25–50 mg daily. b. Esketamine (intranasal; Spravato) i. Approved for use in conjunction with an oral antidepressant. ii. Also approved for major depression with suicidality. iii. Mechanism of action: NMDA (N-methyl-d-aspartate) antagonist. iv. Onset for treating depression symptoms is within hours. v. Dosing occurs in two phases: twice weekly during the induction phase, which lasts for 2 weeks, followed by the maintenance phase, in which dosing is weekly for 4 weeks and then every 1–2 weeks thereafter. vi. Carries black box warnings for sedation, dissociation, abuse and misuse and suicidal thoughts and behaviors. vii. Common adverse reactions: Increased blood pressure, dissociative reactions including derealization and depersonalization, sedation, dizziness, anxiety, nausea, vomiting, and dysgeusia. Long-term use or misuse of ketamine has also been associated with ulcerative or interstitial cystitis. This has not been observed with esketamine in clinical trials but should be monitored. viii. Only available through a REMS program in which patients must be enrolled. Only approved pharmacies can dispense, and agent must be administered in a certified health care setting where patients are observed for at least 2 hours after administration. During this time, mental status and blood pressure must be monitored. Patients cannot drive until the following day. Selective Serotonin Reuptake Inhibitors  GI symptoms Restlessnes Insomnia s Side effects SSRIs Sexual Headache dysfunction  Fluoxetine and sertraline: are the most activating SSRIs Paroxetine and fluvoxamine: are the most sedating. Citalopram and escitalopram: have no appreciable sedating or activating effects.  Serotonin syndrome Causes Symptoms Concomitant use of SSRIs with: Neuromuscular hyperactivity (e.g., Monoamine oxidase inhibitors (MAOIs) myoclonus, rigidity, tremors, Dextromethorphan incoordination). Meperidine Altered mental status (agitation, confusion, hypomania). Tramadol Autonomic instability (hyperthermia, Sympathomimetics diaphoresis). Linezolid lithium TCAs SNRIs  Treatment of serotonin syndrome supportive measures such as: ✔ cooling blankets ✔ respiratory assistance ✔ cyproheptadine; a benzodiazepine for myoclonus ✔ antiseizure medications ✔ nifedipine for hypertension  Other side effects EPS SIADH (syndrome of inappropriate antidiuretic hormone secretion)/ELDERLY PATIENTS. Withdrawal symptoms: flu-like symptoms Citalopram: QTC prolongation These drugs are not as lethal in overdose cases as TCAs Serotonin-Norepinephrine Reuptake Inhibitors Some patients (e.g., treatment nonresponders or those with significant anhedonia) appear to benefit either from agents that affect norepinephrine and serotonin or from combinations of drugs with that effect. All SNRIs can produce serotonin syndrome. SNRIs can cause a withdrawal syndrome similar to the SSRIs and thus should be tapered slowly when discontinued.  Mixed Serotonergic Medications Vilazodone (Viibryd) is an SSRI with partial agonist activity at the serotonin-1A receptor. Vortioxetine (Trintellix) is an SSRI, but its pharmacologic profile differs from other SSRIs. Vortioxetine has additional agonist activity at the serotonin-1A receptor, partial agonist activity at the serotonin-1B receptor, and antagonistic activity at the serotonin-3, serotonin-1D, and serotonin-7 receptors  Serotonin-2A antagonist/reuptake inhibitors Trazodone (Desyrel): ✔ A serotonin reuptake inhibitor that also blocks serotonin-2A receptors. ✔ Trazodone does not cause anticholinergic or cardiotoxic effects as the TCAs, but it still causes OH and sedation. ✔ Trazodone is often used for insomnia but at lower doses than for depression (antihistaminic properties).  Nefazodone (Serzone): ✔ Nefazodone is a serotonin-2A antagonist like trazodone. ✔ It also blocks the reuptake of serotonin and norepinephrine. ✔ Unlike trazodone, nefazodone has minimal effects on sexual function and is less likely to cause OH. ✔ Nefazodone more effective for anxiety associated with depression  Mirtazapine Mirtazapine is an antagonist of presynaptic α2 -autoreceptors and heteroreceptors resulting in an increase in norepinephrine and serotonin release in the synapse. In addition, the drug blocks serotonin-2A (resulting in minimal to no sexual dysfunction, anxiety, or sedation), serotonin-3 (no nausea or GI disturbances), and serotonin-2C (weight gain) receptors. SE: sedative effect, increased appetite, weight gain, constipation, asthenia, abnormal liver function tests, and agranulocytosis may occur.  Bupropion Bupropion is primarily an inhibitor of dopamine and norepinephrine reuptake with minimal effects on serotonin. The most important adverse effect is an increased risk of seizures. SE: insomnia, anxiety, irritability, headache, and decreased appetite. Bupropion may also increase energy and cause psychosis in susceptible individuals. Bupropion may improve sexual function.  Tricyclic Antidepressants TCAs are effective, but adverse effects have limited their use.  TCA serum concentrations can confirm adherence or toxicity. However, this is an infrequent clinical practice. A withdrawal syndrome occurs if these drugs are discontinued too quickly. Symptoms reflect the reversal of anticholinergic effects: lacrimation, nausea, and diarrhea, with insomnia, restlessness, and possible balance problems. Gradual dose reductions help reduce these symptoms.  Monoamine Oxidase Inhibitors Nonselective MAOIs (isocarboxazid, phenelzine, and tranylcypromine). Patients taking MAOIs must be educated and monitored to avoid foods high in tyramine. Drug interactions with MAOIs are considerable and include over-the-counter decongestants, antidepressants, stimulants, and antihypertensives.  When changing a patient from another antidepressant to an MAOI, it is prudent to wait 2 weeks after the antidepressant is discontinued before initiating the MAOI (except for fluoxetine, in which case the waiting period should be 5–6 weeks, and vortioxetine is 3 weeks) to avoid serotonin toxicity. When a patient is changed from an MAOI to another antidepressant, a 2-week washout period is usually adequate. Thank you