Depressive disorders dysphoric disorder

Depression is one of the most common psychiatric disorders. It is characterized by feeling of intense sadness, helplessness, worthlessness, and impaired functioning. Those experiencing a major depressive episode exhibit physical and psychological symptoms, such as appetite disturbances, sleep disturbances, and loss of interest in job, family, and other activities usually enjoyed. A major depressive episode is a depressed or dysphoric (extreme or exaggerated sadness, anxiety, or unhappiness) mood that interferes with daily functioning and includes five or more of the symptoms listed in Display 31-1. 

The current SSRIs in the United States inclnde fluoxetine, fluvoxamine, sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro). All effectively treat major depression. In addition, one or more of the SSRIs has been shown effective in the treatment of dysthymic disorder, the depressive phase of bipolar disorder, premenstrual dysphoric disorder, panic disorder, social phobia, obsessive-compnlsive disorder, bnlimia nervosa, and binge-eating disorder. 

In addition to their proven efficacy in the treatment of all types of depression, the SSRIs have been shown to be the drugs of choice in the treatment of panic disorder, obsessive-compulsive disorder, bulimia nervosa, and as an adjunct to the treatment of alcohol withdrawal and relapse prevention, premenstrual dysphoric disorder and post-traumatic stress disorder. The usefulness of these drugs in treating such a diverse group of disorders reflects the primary role of serotonin in the regulation of sleep, mood, impulsivity and food intake. 

The selective serotonin reuptake inhibitors (SSRI) have been used in adults for a wide variety of disorders, including major depression, social anxiety (social phobia), generalized anxiety disorder (GAD), eating disorders, premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), panic, obsessive-compulsive disorder (OCD), trichotillomania, and migraine headaches. Some of the specific SSRI agents have an approved indication in adults for some of these disorders, as reviewed later in this chapter. The SSRIs have also been tried in children and in adults for symptomatic treatment of pain syndromes, aggressive or irritable ( short fuse ) behavior, and for self-injurious and repetitive behaviors. This chapter will review general aspects of the SSRIs and discuss their approved indications in children and adolescents. 

Some of the growth in antidepressant use may be related to the broad application of these agents for conditions other than major depression. For example, antidepressants have received FDA approvals for the treatment of panic disorder, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). In addition, antidepressants are commonly used to treat pain disorders such as neuropathic pain and the pain associated with fibromyalgia. Some antidepressants are used for treating premenstrual dysphoric disorder (PMDD), mitigating the vasomotor symptoms of menopause, and treating stress urinary incontinence. Thus, antidepressants have a broad... 

Decreased GABAergic effects have also been associated with depression. In vivo evidence of GABAergic dysfunction in patients with depression includes decreased levels of GABA in the CSF, plasma, and occipital cortex (45, 46). Premenstrual dysphoric disorder (PMDD), which is a condition of depressive symptoms prior to menstruation, has been associated with... 

Sanacora G, Mason GE, Rothman DL, Behar K L, Hyder F, Petroff OA, et al. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch. Gen. Psychiatry 1999 56 1043-1047. Epperson CN, Haga K, Mason GE, Sellers E, Gueorguieva R, Zhang W, et al. Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder A proton magnetic resonance spectroscopy study. Arch. Gen. Psychiatry 2002 59 851-858. 

Sertraline hydrochloride is used in the management of depression, obsessive-compulsive disorder (OCD), panic disorder, posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), and social anxiety disorder. 

Clinical uses include major depressions, anxiety states (panic, phobias, social), premenstrual dysphoric disorder, bulimia, OCD, and alcoholism. Withdrawal syndrome following discontinuance in depression nausea, headache, vertigo, malaise. 

The symptoms of premenstrual syndrome (PMS), also called premenstrual dysphoric disorder, include depressed mood, anxiety, affective lability, and anger or irritability.79 Since low serotonin levels are thought to be involved in the etiology of depression, aggression, and impulsivity,80 specific serotonin reuptake inhibitors have been tested in PMS. The SSRI fluoxetine was found to be better than placebo.81 Since chronic treatment with SSRIs can influence many neuron systems other than serotonin,82 Steinberg et al.83 designed a study using tryptophan, relatively specific for its effect on serotonin, on the effects of symptoms of PMS. In a randomized controlled clinical trial, 37... 

The diversity of action on brain chemistry provides evidence that St. John s wort can exercise a significant effect on a depressed person s brain. However, since most of these actions are not nearly as intense as those found in SSRIs and other antidepressants, it makes sense that St. John s wort cannot cure severe depression. Thus St. John s wort seems best suited for slight to moderate depression, anxiety, or stress. It has also been recognized as a possible cure for premenstrual dysphoric disorder. However, users should be cautioned that appropriate doses of St. John s wort are much more variable than those of standard antidepressants. 

Acute mania as part of bipolar I disorder is supposed to result from overexcitation of limbic neurons. This can arise either from loss of inhibitory tonic orbitofrontal control of limbic neurons or from various intra- and intercellular alterations (the full mechanism is unknown as yet). Manic episodes are often classified into euphoric (classical), dysphoric, mixed (along with clinical manifestations of major depressive disorder), mania with psychotic/catatonic features, and mania with a rapid cycling course of the disease. 

Monoamine oxidase inhibitors, such as SSRIs, have been shown to be effective in the treatment of depression, and they have become among the most widely used prescription drugs in the United States. Prozac is used not only to treat major depressive disorders but also bulimia nervosa, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder. Multiple serotonin receptor subtypes are involved. Specific serotonin receptor subtype agonists and antagonists have been radiolabeled with positron-emitting tracers to assess the state of the serotonergic system. 

In contrast to MDD, the bipolar disorders consist of episodes of depression and episodes of hypomania or mania. This poses a problem for treating the depressed phase of this illness, becanse, as noted earlier, antidepressants can trigger hypomania, mania, or mixed dysphoric mania and can increase the freqnency of manic episodes. Therefore, the hallmark of treating BPAD is the nse of mood stabilizers, with and withont snpplemental antidepressant therapy. Please refer to Table 3.16 for a comparison of the traditional mood stabilizers. 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

A 34-year-old woman with a history of polysubstance dependence (alcohol, cannabis, and cocaine), depressive episodes associated with multiple suicide attempts, and borderline personality disorder, who had been incarcerated after conviction on charges of physical assault and possession of controlled substances, complained of difficulty in sleeping, poor impulse control, irritability, and depressed mood. She was given oral quetiapine 600 mg/day. On one occasion, she crushed two 300-mg tablets, dissolved them in water, boiled them, drew the solution through a cotton swab, and injected the solution intravenously. Apart from having the best sleep I ever had she described no dysphoric, euphoric, or other effects. She admitted to previous intranasal abuse of crushed quetiapine tablets. 

Beginning with Kraepelin s (1921) systematic classification of dysphoric mania, considerable attention has been paid to mixed states of bipolar disorder. Kraepelin s model was based on variable symptom patterns expressed in three areas, mood, thought, and motor activity. Once considered to be uncommon, current estimates suggest that the prevalence rate for dysphoric, or mixed mania, is approximately 30 percent (McElroy et al. 1992). Debate continues regarding the status of mixed mania as a distinct affective state versus a form, or stage, of typical mania. However, there is convincing evidence to support the opinion that mixed episodes can be more severe, chronic, and difficult to treat than pure manic or depressive episodes (Clothier,... 

One of the biggest problems for many clinical professionals who work with these clients is the lack of clarity and problems in semantics in defining what the term depression actually means. For many individuals, depression can mean feeling sad, blue, or down in the dumps, whereas for others there are clearly established criteria that reflect consistent patterns, signs, and symptoms relative to a mood disorder (Gitlin, 19%). Furthermore, some form of depression (also referred to as dysphoric mood) is present in virtually all mental health conditions. The only possible exceptions to this are clients who suffer from mania, certain forms of schizophrenia, or dementia (Gitlin, 1996). 

Another risk of antidepressants in vulnerable patients (particularly those with unrecognized bipolar depression) is switching, sometimes suddenly, from depression to hypomanic or manic excitement, or mixed, dysphoric-agitated, manic-depressive states. To some extent this effect is dose-related and is somewhat more likely in adults treated with tricyclic antidepressants than with serotonin reuptake inhibitors, bupropion, and perhaps with MAO inhibitors. Risk of mania with newer sedating antidepressants, including nefazodone and mirtazapine, also may be relatively low, but some risk of inducing mania can be expected with any treatment that elevates mood, including in children with unsuspected bipolar disorder. 

Bipolar affective is when the patient undergoes moods swings from manic (euphoric) to depressive (dysphoric). Lithium is prescribed for bipolar affective disorders. 

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