Depression treatment phases

FIGURE 36.1 Major depressive disorder—acute treatment phase. 

It is recommended that adult patients with second episodes of depression and who fulfill the criteria for maintenance therapy noted above be maintained for several years (up to 5 years in adult studies), using the same dosage of the antidepressant used to achieve clinical remission during the acute-treatment phase. Maintenance therapy for patients with three or more episodes of MDD, patients with second episodes associated with psychosis, severe impairment, and severe suicidality, and those who proved very difficult to treat should be considered for longer periods of time, even for the life of the patient (AACAP, 1998). 

FI6U RE 6 5 B. Mood analogue ratings showing unequivocal response to nimodipine after placebo substitution in a patient with bipolar 11 disorder with ultra-ultrarapid cycbng. Mean deviation above 13 for the entire treatment phase (not just the 1 month illustrated). M = mania D = depression T = euthymia. 

The depressed prices of most metals in world markets in the 1980s and early 1990s have slowed the development of new metal extraction processes, although the search for improved extractants continues. There is a growing interest in the use of extraction for recovery of metals from effluent streams, for example the wastes from pickling plants and electroplating (qv) plants (276). Recovery of metals from Hquid effluent has been reviewed (277), and an AM-MAR concept for metal waste recovery has recentiy been reported (278). Possible appHcations exist in this area for Hquid membrane extraction (88) as weU as conventional extraction. Other schemes proposed for effluent treatment are a wetted fiber extraction process (279) and the use of two-phase aqueous extraction (280). 

C, is the concentration of impurity or minor component in the solid phase, and Cf is the impurity concentration in the hquid phase. The distribution coefficient generally varies with composition. The value of k is greater than I when the solute raises the melting point and less than I when the melting point is depressed. In the regions near pure A or B the hquidus and solidus hues become linear i.e., the distribution coefficient becomes constant. This is the basis for the common assumption of constant k in many mathematical treatments of fractional solidification in which ultrapure materials are obtained. 

Ticlopidine inhibits the P2Yj2 platelet ADP receptor, thus inhibiting ADP-dependent activation of the GP Ilb/IIIa receptor. It has a slow onset of action and takes 3-7 days to reach its maximal antiplatelet effect. It is inactive in vitro and must undergo activation by the hepatic cytochrome p450 enzyme system. Secondary prevention trials have found that ticlopidine-treated patients have an estimated RRR of 33% for the composite endpoint of stroke, myocardial infarction, or vascular death after ischemic stroke. Significant adverse effects include bone marrow depression, rash, diarrhea, and thrombotic thrombocytopenic purpura. No clinical trials have studied ticlopidine for the treatment of stroke in the acute phase. 

The functions of these different phases of sleep are not at all clear but chronic sleep deprivation does eventually lead to death. It seems to be the slow-wave component of sleep (SWS) that is vital and it is thought to serve a restorative purpose. This would be consistent with its greater occurrence during the early stages of the sleep cycle when hormone secretion supports anabolic metabolism. If subjects are wakened every time they enter a period of REM sleep (evidenced by the EEG) there appears to be no overt harmful effect on their behaviour. In fact, REM sleep deprivation has even been used, with some claims of success, as a treatment for minor depression. However, there is an unproven belief that REM sleep is important for memory consolidation. 

Jiang, R. H., Shu, L., Zhang, H. Y. et al. (2006). A phase II randomized double blind multi-centers and parallel control clinical trial for bupropion SR in the treatment of depressive disorders. Chinese Journal of New Drugs, 15(2), 128-31. 

One of the main reasons for excluding patients from clinical trials is to make it easier to find differences between the drug and the placebo.26 There are two ways in which excluding some patients from the trials can help accomplish this aim. One is to eliminate those who are most likely to respond to a placebo. To accomplish this goal, patients are excluded from clinical trials if they have only been depressed for a short time, if they are only mildly depressed or if they respond to placebo treatment during the placebo run-in phase. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

Both enantiomers and the racemate of l-(3,4-dichlorophenyl)-3-azabicyclo [3.1.0]hexane, 27a-c, have been reported to be in development. The racemate, DOV 216,303, inhibits the reuptake of NE, 5-HT and DA with IC50 values of 20, 14 and 78 nM, respectively [85]. DOV 216,303 is active in tests predictive of antidepressant activity, including the mouse FST (minimum effective dose = lOmg/kg), reversal of tetrabenazine-induced ptosis and locomotor depression. DOV 216,303 was also reported to be well tolerated in phase I clinical trials [85,86], In a phase II study designed to explore safety and tolerability in depressed individuals, patients received either DOV 216,303 (50 mg, b.i.d.) or citalopram (20 mg, b.i.d.) for two weeks [85]. It was found that the side effect profile was not remarkably different between the two treatment groups. In addition, time-dependent reductions in Hamilton Depression Scores (HAM-D) were similar for both groups. 

Key parameters include temperature, pounds of steam injected (or similar factors for air), and duration and depth of treatment. Steam at a pressure 3.5 to 4.2 kg/cm2 (50 to 60 psi) can heat contaminated soil to 155°C (310°F). The recovery process involves the use of wells to depress the water table and ensure capture of released free-phase NAPLs and vapor-phase hydrocarbons at or near the surface. A conceptual schematic is shown in Figure 10.8. 

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. 

The first decision when beginning acute phase treatment is choosing the primary treatment modality psychotherapy, medication, or both. Several short-term therapies including CBT, IPT, brief psychodynamic therapy, and marital therapy are effective treatments in mild-to-moderate cases of depression without added antidepressant treatment. This is a viable alternative that many patients may prefer. 

Maintenance Phase Treatment. The purpose of this phase of treatment is to provide protection against a recurrence of the illness. In contrast to a relapse, a recurrence is the development of a new episode of depression after the complete resolution of a prior episode. Though theoretically defensible, the distinction between a relapse and recurrence is often vague. 

It is common for both the depressive and manic phases to occur simultaneously in what is termed a mixed state or dysphoric mania. During these mixed episodes, the patient s mood is characterized by symptoms of both a depression and mania. Mixed episodes often have a poorer outcome than classic euphoric mania and, as a rule, respond better to certain anticonvulsants and atypical antipsychotic drugs than to lithium. As many as 50% of admissions to inpatient psychiatric facilities for the treatment of manic episodes appear to be for mixed manic states. The recognition... 

Depressive Episodes. The emphasis of treatment research in bipolar illness has understandably been on the management of manic and hypomanic phases of these disorders. However, there is clearly room for improvement in the treatment of the depressive phase of BPAD as well. Depression accounts for the majority of BPAD episodes in both men and women, especially the latter. Furthermore, bipolar depression is associated with an increased risk of suicide. 

The first step in managing bipolar depression is, of course, to arrive at the correct diagnosis. Producing a life chart that delineates the duration, severity, and frequency of illness episodes is critical to treatment selection. Treatment that focuses on the management of the depressive phase is especially important for patients with three or more depressive episodes, particularly severe depressions, or significant subsyn-dromal depressive symptoms between episodes. 

During the maintenance phase, treatment can be fine-tnned. If persistent side effects (especially EPS) are a problem, then the antipsychotic can be gradnally switched or conntermeasures snch as anticholinergic therapy can be taken. In addition, maintenance therapy is also an appropriate time to address the less dramatic bnt nonetheless tronblesome symptoms snch as a mood distnrbance. Antidepressants are often used to treat depressed mood in patients with schizophrenia. Likewise, benzodiazepines are commonly nsed with an antipsychotic to treat persistent yet subsyndromal anxiety in schizophrenia patients. 

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