DEPRESSION AND ANXIETY

• Depressive and anxiety disorders

  Primary clinical manifestations are significant depression of mood and impairment of function
• Disorders that overlap with depressive disorders

  • Panic-agoraphobia syndrome
  • Severe phobias
  • Generalized anxiety disorder
  • Social anxiety disorder
  • Posttraumatic stress disorder
  • Obsessive-compulsive disorder
• Psychosis


  Disordered or delusional thinking and perceptions that often are congruent with the predominant mood
• Clinical depression


  Must be distinguished from normal grief, sadness, disappointment, and the dysphoria or demoralization often associated with medical illness
• Major depression


  • Feelings of intense sadness and despair, mental slowing and loss of concentration, pessimistic worry, lack of pleasure, self-deprecation, and variable agitation or hostility
  • Physical changes including insomnia or hypersomnia, altered eating patterns, decreased energy and libido, and disruption of normal circadian and ultradian rhythms
• 10% to 15% of individuals with severe clinical depression, and up to 25% of those with bipolar disorder, display suicidal behavior at some time
• Antidepressant drugs


  Used to treat depressed patients, or, in severe or treatment-resistant cases, electroconvulsive therapy (ECT)
• Efficacy of other forms of biological treatment of depression (e.g., magnetic stimulation of the brain, or electrical stimulation of the vagus nerve) has not been well established
• Major disorders of mood or affect

  • Major depression
  • Bipolar disorder
• Lifetime prevalence of bipolar disorder

  1% to 2% for type I (with mania), about twice that rate if cases of recurrent depression with milder upswings of mood (hypomania) are included (type II bipolar disorder)
• Lifetime risk for major depression

  5% to 10%, approximately twice the risk in women than in men
• Bipolar disorder


  • Marked by a high likelihood of recurrences of severe depression and manic excitement, often with psychotic features
• Bipolar disorder and major depression are associated with increased risk of self-harm or suicide as well as increased mortality from stress sensitive general medical conditions, medical complications of comorbid abuse of alcohol or illicit drugs, or from accidents
• Norepinephrine reuptake inhibitors


  Relatively selective inhibitors like atomoxetine and reboxetine, share many of the actions of older inhibitors of norepinephrine transport such as desipramine
• Antidepressant medications


  • Tricyclic antidepressants
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Atypical modern agents
• Tricyclic antidepressants


  Largely supplanted by the newer, less-toxic SSRIs and other atypical modern agents, which now are accepted broadly as drugs of first choice
• MAO inhibitors


  Commonly reserved for patients who fail to respond to vigorous trials of at least one of the newer agents and a standard tricyclic antidepressant, administered alone or with lithium or low doses of triiodothyronine to enhance overall therapeutic effectiveness
• Secondary-amine tricyclics


  Particularly nortriptyline and desipramine, can be considered as an alternative or a second choice for elderly or medically ill patients, particularly if administered in moderate, divided doses
• Patients with severe, prolonged, disabling, psychotic, suicidal, or bipolar depression require vigorous and prompt medical intervention
• Under diagnosis of depressive illnesses arises in part from the sometimes misleading clinical presentation of many depressed patients with nonspecific somatic complaints, anxiety, or insomnia
• Under treatment arose from the reluctance of physicians to prescribe potentially toxic or pharmacologically complicated tricyclic or MAO inhibitor antidepressants, especially to medically ill or elderly patients
• This pattern is changing with the wide acceptance of less-toxic and better-accepted antidepressants among the serotonin reuptake inhibitors and atypical agents
• Valproic acid (VPA)


  An acidic chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression
• Mechanism of action of valproic acid

  1. Enhances neurotransmission of GABA (by inhibiting GABA transaminase)

  2. Blocks voltage-gated sodium channels and T-type calcium channels

  3. Inhibits the enzyme histone deacetylase 1 (HDAC1), hence it is a histone deacetylase inhibitor
• Therapeutic uses of valproic acid

  • Control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, juvenile myoclonic epilepsy, and the seizures associated with Lennox-Gastaut syndrome
  • Treatment of myoclonus
  • Second-line treatment of status epilepticus
  • Treatment of neuropathic pain
  • Treatment of manic episodes associated with bipolar disorder
  • Prophylaxis of migraine headaches
  • Controlling behavioral disturbances in dementia patients
• Schizophrenia


  A mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness
• Causes of schizophrenia


  • Genes may play a role, and certain events may trigger schizophrenia in people who are at risk for it because of their genes
• Symptoms of schizophrenia


  • Irritable or tense feeling
  • Trouble concentrating
  • Trouble sleeping
  • Bizarre behaviors
  • Hallucinations
  • Isolation
  • Lack of emotion (flat affect)
  • Problems paying attention
  • Delusions
  • Thoughts that "jump" between different topics ("loose associations")
• Antipsychotic medications are the most effective treatment for schizophrenia
• Chlorpromazine


  A low-potency typical antipsychotic used in the treatment of both acute and chronic psychoses, including schizophrenia and the manic phase of bipolar disorder as well as amphetamine-induced psychoses
• Mechanism of action of chlorpromazine

  Works on a variety of receptors in the central nervous system, producing anticholinergic, antidopaminergic, antihistaminic, and weak antiadrenergic effects
• Therapeutic uses of chlorpromazine

  • Antipsychotic treatment
  • Treatment of porphyria
  • Treatment of tetanus
  • Short term management of severe anxiety and aggressive episodes
  • Treatment of resistant and severe hiccups, severe nausea/emesis and preanesthetic conditioning
  • Treatment of symptoms of delirium in medically hospitalized AIDS patients
• Side effects of many antipsychotics

  • Drowsiness
  • Dizziness when changing positions
  • Blurred vision
  • Rapid heartbeat
  • Sensitivity to the sun
  • Skin rashes
  • Menstrual problems for women
• Alzheimer's disease


  A progressive neurologic disease of the brain leading to the irreversible loss of neurons and the loss of intellectual abilities, including memory and reasoning, which become severe enough to impede social or occupational functioning
• Early symptoms of Alzheimer's disease

  • Difficulty remembering newly learned information
  • Disorientation
  • Mood and behavior changes
  • Deepening confusion about events, time and place
  • Unfounded suspicions about family, friends and professional caregivers
  • More serious memory loss and behavior changes
  • Difficulty speaking, swallowing and walking
• Other symptoms of Alzheimer's disease

  • Change in sleep patterns, often waking up at night
  • Delusions, depression, agitation
  • Difficulty doing basic tasks, such as preparing meals, choosing proper clothing, and driving
  • Difficulty reading or writing
  • Forgetting details about current events
  • Forgetting events in your own life history, losing awareness of who you are
  • Hallucinations, arguments, striking out, and violent behavior
  • Poor judgment and loss of ability to recognize danger
  • Using the wrong word, mispronouncing words, speaking in confusing sentences
  • Withdrawing from social contact
  • Inability to understand language, recognize family members, or perform basic activities of daily living
• Cause of Alzheimer's disease

  The "amyloid cascade hypothesis" is the most widely discussed and researched hypothesis, which suggests excess production or insufficient removal of the Aβ protein fragment in the brain
• Donepezil


  A centrally acting reversible acetylcholinesterase inhibitor used in the palliative treatment of mild to moderate Alzheimer's disease
• Side effects of Donepezil (Aricept)


  • Slow heartbeat and fainting, more often in people with heart problems
  • Seizures
  • Difficulty passing urine
  • Worsening of lung problems, including asthma
• Hallucination


  A perception in the absence of a stimulus, which is vivid, substantial, and located in external objective space, distinct from dreaming, illusion, imagery, and pseudo hallucination